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

Gespeichert in:

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:	genetics oral health child molecular epidemiology

Übergeordnetes Werk:	In: Genes - MDPI AG, 2010, 14(2022), 1, p 59
Übergeordnetes Werk:	volume:14 ; year:2022 ; number:1, p 59

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/genes14010059

Katalog-ID:	DOAJ081798733

Internformat


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

Indexfelder

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

Nicht das Richtige dabei?

Schreiben Sie uns!

Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?