Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study
Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral H...
Ausführliche Beschreibung
Autor*in: |
Ekaterina Orlova [verfasserIn] Tom Dudding [verfasserIn] Jonathan M. Chernus [verfasserIn] Rasha N. Alotaibi [verfasserIn] Simon Haworth [verfasserIn] Richard J. Crout [verfasserIn] Myoung Keun Lee [verfasserIn] Nandita Mukhopadhyay [verfasserIn] Eleanor Feingold [verfasserIn] Steven M. Levy [verfasserIn] Daniel W. McNeil [verfasserIn] Betsy Foxman [verfasserIn] Robert J. Weyant [verfasserIn] Nicholas J. Timpson [verfasserIn] Mary L. Marazita [verfasserIn] John R. Shaffer [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2022 |
---|
Schlagwörter: |
---|
Übergeordnetes Werk: |
In: Genes - MDPI AG, 2010, 14(2022), 1, p 59 |
---|---|
Übergeordnetes Werk: |
volume:14 ; year:2022 ; number:1, p 59 |
Links: |
---|
DOI / URN: |
10.3390/genes14010059 |
---|
Katalog-ID: |
DOAJ081798733 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | DOAJ081798733 | ||
003 | DE-627 | ||
005 | 20240414133339.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230310s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/genes14010059 |2 doi | |
035 | |a (DE-627)DOAJ081798733 | ||
035 | |a (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
050 | 0 | |a QH426-470 | |
100 | 0 | |a Ekaterina Orlova |e verfasserin |4 aut | |
245 | 1 | 0 | |a Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. | ||
650 | 4 | |a genetics | |
650 | 4 | |a oral health | |
650 | 4 | |a child | |
650 | 4 | |a molecular epidemiology | |
653 | 0 | |a Genetics | |
700 | 0 | |a Tom Dudding |e verfasserin |4 aut | |
700 | 0 | |a Jonathan M. Chernus |e verfasserin |4 aut | |
700 | 0 | |a Rasha N. Alotaibi |e verfasserin |4 aut | |
700 | 0 | |a Simon Haworth |e verfasserin |4 aut | |
700 | 0 | |a Richard J. Crout |e verfasserin |4 aut | |
700 | 0 | |a Myoung Keun Lee |e verfasserin |4 aut | |
700 | 0 | |a Nandita Mukhopadhyay |e verfasserin |4 aut | |
700 | 0 | |a Eleanor Feingold |e verfasserin |4 aut | |
700 | 0 | |a Steven M. Levy |e verfasserin |4 aut | |
700 | 0 | |a Daniel W. McNeil |e verfasserin |4 aut | |
700 | 0 | |a Betsy Foxman |e verfasserin |4 aut | |
700 | 0 | |a Robert J. Weyant |e verfasserin |4 aut | |
700 | 0 | |a Nicholas J. Timpson |e verfasserin |4 aut | |
700 | 0 | |a Mary L. Marazita |e verfasserin |4 aut | |
700 | 0 | |a John R. Shaffer |e verfasserin |4 aut | |
773 | 0 | 8 | |i In |t Genes |d MDPI AG, 2010 |g 14(2022), 1, p 59 |w (DE-627)614096537 |w (DE-600)2527218-4 |x 20734425 |7 nnns |
773 | 1 | 8 | |g volume:14 |g year:2022 |g number:1, p 59 |
856 | 4 | 0 | |u https://doi.org/10.3390/genes14010059 |z kostenfrei |
856 | 4 | 0 | |u https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 |z kostenfrei |
856 | 4 | 0 | |u https://www.mdpi.com/2073-4425/14/1/59 |z kostenfrei |
856 | 4 | 2 | |u https://doaj.org/toc/2073-4425 |y Journal toc |z kostenfrei |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_DOAJ | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 14 |j 2022 |e 1, p 59 |
author_variant |
e o eo t d td j m c jmc r n a rna s h sh r j c rjc m k l mkl n m nm e f ef s m l sml d w m dwm b f bf r j w rjw n j t njt m l m mlm j r s jrs |
---|---|
matchkey_str |
article:20734425:2022----::soitooeryhlhocrewtbtetseeetraeanlssfeoeiesoitosuisn |
hierarchy_sort_str |
2022 |
callnumber-subject-code |
QH |
publishDate |
2022 |
allfields |
10.3390/genes14010059 doi (DE-627)DOAJ081798733 (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 DE-627 ger DE-627 rakwb eng QH426-470 Ekaterina Orlova verfasserin aut Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. genetics oral health child molecular epidemiology Genetics Tom Dudding verfasserin aut Jonathan M. Chernus verfasserin aut Rasha N. Alotaibi verfasserin aut Simon Haworth verfasserin aut Richard J. Crout verfasserin aut Myoung Keun Lee verfasserin aut Nandita Mukhopadhyay verfasserin aut Eleanor Feingold verfasserin aut Steven M. Levy verfasserin aut Daniel W. McNeil verfasserin aut Betsy Foxman verfasserin aut Robert J. Weyant verfasserin aut Nicholas J. Timpson verfasserin aut Mary L. Marazita verfasserin aut John R. Shaffer verfasserin aut In Genes MDPI AG, 2010 14(2022), 1, p 59 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2022 number:1, p 59 https://doi.org/10.3390/genes14010059 kostenfrei https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 kostenfrei https://www.mdpi.com/2073-4425/14/1/59 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1, p 59 |
spelling |
10.3390/genes14010059 doi (DE-627)DOAJ081798733 (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 DE-627 ger DE-627 rakwb eng QH426-470 Ekaterina Orlova verfasserin aut Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. genetics oral health child molecular epidemiology Genetics Tom Dudding verfasserin aut Jonathan M. Chernus verfasserin aut Rasha N. Alotaibi verfasserin aut Simon Haworth verfasserin aut Richard J. Crout verfasserin aut Myoung Keun Lee verfasserin aut Nandita Mukhopadhyay verfasserin aut Eleanor Feingold verfasserin aut Steven M. Levy verfasserin aut Daniel W. McNeil verfasserin aut Betsy Foxman verfasserin aut Robert J. Weyant verfasserin aut Nicholas J. Timpson verfasserin aut Mary L. Marazita verfasserin aut John R. Shaffer verfasserin aut In Genes MDPI AG, 2010 14(2022), 1, p 59 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2022 number:1, p 59 https://doi.org/10.3390/genes14010059 kostenfrei https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 kostenfrei https://www.mdpi.com/2073-4425/14/1/59 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1, p 59 |
allfields_unstemmed |
10.3390/genes14010059 doi (DE-627)DOAJ081798733 (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 DE-627 ger DE-627 rakwb eng QH426-470 Ekaterina Orlova verfasserin aut Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. genetics oral health child molecular epidemiology Genetics Tom Dudding verfasserin aut Jonathan M. Chernus verfasserin aut Rasha N. Alotaibi verfasserin aut Simon Haworth verfasserin aut Richard J. Crout verfasserin aut Myoung Keun Lee verfasserin aut Nandita Mukhopadhyay verfasserin aut Eleanor Feingold verfasserin aut Steven M. Levy verfasserin aut Daniel W. McNeil verfasserin aut Betsy Foxman verfasserin aut Robert J. Weyant verfasserin aut Nicholas J. Timpson verfasserin aut Mary L. Marazita verfasserin aut John R. Shaffer verfasserin aut In Genes MDPI AG, 2010 14(2022), 1, p 59 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2022 number:1, p 59 https://doi.org/10.3390/genes14010059 kostenfrei https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 kostenfrei https://www.mdpi.com/2073-4425/14/1/59 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1, p 59 |
allfieldsGer |
10.3390/genes14010059 doi (DE-627)DOAJ081798733 (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 DE-627 ger DE-627 rakwb eng QH426-470 Ekaterina Orlova verfasserin aut Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. genetics oral health child molecular epidemiology Genetics Tom Dudding verfasserin aut Jonathan M. Chernus verfasserin aut Rasha N. Alotaibi verfasserin aut Simon Haworth verfasserin aut Richard J. Crout verfasserin aut Myoung Keun Lee verfasserin aut Nandita Mukhopadhyay verfasserin aut Eleanor Feingold verfasserin aut Steven M. Levy verfasserin aut Daniel W. McNeil verfasserin aut Betsy Foxman verfasserin aut Robert J. Weyant verfasserin aut Nicholas J. Timpson verfasserin aut Mary L. Marazita verfasserin aut John R. Shaffer verfasserin aut In Genes MDPI AG, 2010 14(2022), 1, p 59 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2022 number:1, p 59 https://doi.org/10.3390/genes14010059 kostenfrei https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 kostenfrei https://www.mdpi.com/2073-4425/14/1/59 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1, p 59 |
allfieldsSound |
10.3390/genes14010059 doi (DE-627)DOAJ081798733 (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 DE-627 ger DE-627 rakwb eng QH426-470 Ekaterina Orlova verfasserin aut Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. genetics oral health child molecular epidemiology Genetics Tom Dudding verfasserin aut Jonathan M. Chernus verfasserin aut Rasha N. Alotaibi verfasserin aut Simon Haworth verfasserin aut Richard J. Crout verfasserin aut Myoung Keun Lee verfasserin aut Nandita Mukhopadhyay verfasserin aut Eleanor Feingold verfasserin aut Steven M. Levy verfasserin aut Daniel W. McNeil verfasserin aut Betsy Foxman verfasserin aut Robert J. Weyant verfasserin aut Nicholas J. Timpson verfasserin aut Mary L. Marazita verfasserin aut John R. Shaffer verfasserin aut In Genes MDPI AG, 2010 14(2022), 1, p 59 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2022 number:1, p 59 https://doi.org/10.3390/genes14010059 kostenfrei https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 kostenfrei https://www.mdpi.com/2073-4425/14/1/59 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1, p 59 |
language |
English |
source |
In Genes 14(2022), 1, p 59 volume:14 year:2022 number:1, p 59 |
sourceStr |
In Genes 14(2022), 1, p 59 volume:14 year:2022 number:1, p 59 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
genetics oral health child molecular epidemiology Genetics |
isfreeaccess_bool |
true |
container_title |
Genes |
authorswithroles_txt_mv |
Ekaterina Orlova @@aut@@ Tom Dudding @@aut@@ Jonathan M. Chernus @@aut@@ Rasha N. Alotaibi @@aut@@ Simon Haworth @@aut@@ Richard J. Crout @@aut@@ Myoung Keun Lee @@aut@@ Nandita Mukhopadhyay @@aut@@ Eleanor Feingold @@aut@@ Steven M. Levy @@aut@@ Daniel W. McNeil @@aut@@ Betsy Foxman @@aut@@ Robert J. Weyant @@aut@@ Nicholas J. Timpson @@aut@@ Mary L. Marazita @@aut@@ John R. Shaffer @@aut@@ |
publishDateDaySort_date |
2022-01-01T00:00:00Z |
hierarchy_top_id |
614096537 |
id |
DOAJ081798733 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ081798733</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414133339.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230310s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3390/genes14010059</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ081798733</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJbc17d90df8e64e32a44c858b465ac630</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Ekaterina Orlova</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">oral health</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">child</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">molecular epidemiology</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tom Dudding</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jonathan M. Chernus</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rasha N. Alotaibi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Simon Haworth</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Richard J. Crout</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Myoung Keun Lee</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nandita Mukhopadhyay</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Eleanor Feingold</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Steven M. Levy</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Daniel W. McNeil</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Betsy Foxman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Robert J. Weyant</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nicholas J. Timpson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mary L. Marazita</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">John R. Shaffer</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Genes</subfield><subfield code="d">MDPI AG, 2010</subfield><subfield code="g">14(2022), 1, p 59</subfield><subfield code="w">(DE-627)614096537</subfield><subfield code="w">(DE-600)2527218-4</subfield><subfield code="x">20734425</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:14</subfield><subfield code="g">year:2022</subfield><subfield code="g">number:1, p 59</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3390/genes14010059</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.mdpi.com/2073-4425/14/1/59</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2073-4425</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">14</subfield><subfield code="j">2022</subfield><subfield code="e">1, p 59</subfield></datafield></record></collection>
|
callnumber-first |
Q - Science |
author |
Ekaterina Orlova |
spellingShingle |
Ekaterina Orlova misc QH426-470 misc genetics misc oral health misc child misc molecular epidemiology misc Genetics Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study |
authorStr |
Ekaterina Orlova |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)614096537 |
format |
electronic Article |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
collection |
DOAJ |
remote_str |
true |
callnumber-label |
QH426-470 |
illustrated |
Not Illustrated |
issn |
20734425 |
topic_title |
QH426-470 Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study genetics oral health child molecular epidemiology |
topic |
misc QH426-470 misc genetics misc oral health misc child misc molecular epidemiology misc Genetics |
topic_unstemmed |
misc QH426-470 misc genetics misc oral health misc child misc molecular epidemiology misc Genetics |
topic_browse |
misc QH426-470 misc genetics misc oral health misc child misc molecular epidemiology misc Genetics |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Genes |
hierarchy_parent_id |
614096537 |
hierarchy_top_title |
Genes |
isfreeaccess_txt |
true |
familylinks_str_mv |
(DE-627)614096537 (DE-600)2527218-4 |
title |
Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study |
ctrlnum |
(DE-627)DOAJ081798733 (DE-599)DOAJbc17d90df8e64e32a44c858b465ac630 |
title_full |
Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study |
author_sort |
Ekaterina Orlova |
journal |
Genes |
journalStr |
Genes |
callnumber-first-code |
Q |
lang_code |
eng |
isOA_bool |
true |
recordtype |
marc |
publishDateSort |
2022 |
contenttype_str_mv |
txt |
author_browse |
Ekaterina Orlova Tom Dudding Jonathan M. Chernus Rasha N. Alotaibi Simon Haworth Richard J. Crout Myoung Keun Lee Nandita Mukhopadhyay Eleanor Feingold Steven M. Levy Daniel W. McNeil Betsy Foxman Robert J. Weyant Nicholas J. Timpson Mary L. Marazita John R. Shaffer |
container_volume |
14 |
class |
QH426-470 |
format_se |
Elektronische Aufsätze |
author-letter |
Ekaterina Orlova |
doi_str_mv |
10.3390/genes14010059 |
author2-role |
verfasserin |
title_sort |
association of early childhood caries with bitter taste receptors: a meta-analysis of genome-wide association studies and transcriptome-wide association study |
callnumber |
QH426-470 |
title_auth |
Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study |
abstract |
Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. |
abstractGer |
Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. |
abstract_unstemmed |
Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
container_issue |
1, p 59 |
title_short |
Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study |
url |
https://doi.org/10.3390/genes14010059 https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630 https://www.mdpi.com/2073-4425/14/1/59 https://doaj.org/toc/2073-4425 |
remote_bool |
true |
author2 |
Tom Dudding Jonathan M. Chernus Rasha N. Alotaibi Simon Haworth Richard J. Crout Myoung Keun Lee Nandita Mukhopadhyay Eleanor Feingold Steven M. Levy Daniel W. McNeil Betsy Foxman Robert J. Weyant Nicholas J. Timpson Mary L. Marazita John R. Shaffer |
author2Str |
Tom Dudding Jonathan M. Chernus Rasha N. Alotaibi Simon Haworth Richard J. Crout Myoung Keun Lee Nandita Mukhopadhyay Eleanor Feingold Steven M. Levy Daniel W. McNeil Betsy Foxman Robert J. Weyant Nicholas J. Timpson Mary L. Marazita John R. Shaffer |
ppnlink |
614096537 |
callnumber-subject |
QH - Natural History and Biology |
mediatype_str_mv |
c |
isOA_txt |
true |
hochschulschrift_bool |
false |
doi_str |
10.3390/genes14010059 |
callnumber-a |
QH426-470 |
up_date |
2024-07-03T22:01:06.674Z |
_version_ |
1803596927257804800 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ081798733</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414133339.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230310s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3390/genes14010059</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ081798733</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJbc17d90df8e64e32a44c858b465ac630</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Ekaterina Orlova</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total <i<N</i< = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (<i<p</i<-values < 3.09 × 10<sup<−6</sup<; <i<CDH17</i<, <i<TAS2R43</i<, <i<SMIM10L1</i<, <i<TAS2R14</i<). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by <i<TAS2R14</i<, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, <i<Streptococcus mutans</i< and <i<Staphylococcus aureus</i<. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">oral health</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">child</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">molecular epidemiology</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tom Dudding</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jonathan M. Chernus</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rasha N. Alotaibi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Simon Haworth</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Richard J. Crout</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Myoung Keun Lee</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nandita Mukhopadhyay</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Eleanor Feingold</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Steven M. Levy</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Daniel W. McNeil</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Betsy Foxman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Robert J. Weyant</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nicholas J. Timpson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mary L. Marazita</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">John R. Shaffer</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Genes</subfield><subfield code="d">MDPI AG, 2010</subfield><subfield code="g">14(2022), 1, p 59</subfield><subfield code="w">(DE-627)614096537</subfield><subfield code="w">(DE-600)2527218-4</subfield><subfield code="x">20734425</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:14</subfield><subfield code="g">year:2022</subfield><subfield code="g">number:1, p 59</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3390/genes14010059</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/bc17d90df8e64e32a44c858b465ac630</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.mdpi.com/2073-4425/14/1/59</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2073-4425</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">14</subfield><subfield code="j">2022</subfield><subfield code="e">1, p 59</subfield></datafield></record></collection>
|
score |
7.399398 |