A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy
Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk,...
Ausführliche Beschreibung
Autor*in: |
Liu, Shuwei [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Anmerkung: |
© The Author(s) 2023 |
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Übergeordnetes Werk: |
Enthalten in: Epigenetics Communications - BioMed Central, 2021, 3(2023), 1 vom: 26. Jan. |
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Übergeordnetes Werk: |
volume:3 ; year:2023 ; number:1 ; day:26 ; month:01 |
Links: |
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DOI / URN: |
10.1186/s43682-022-00014-w |
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Katalog-ID: |
SPR05138955X |
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100 | 1 | |a Liu, Shuwei |e verfasserin |0 (orcid)0000-0002-4089-8359 |4 aut | |
245 | 1 | 2 | |a A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy |
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520 | |a Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. | ||
650 | 4 | |a Preeclampsia |7 (dpeaa)DE-He213 | |
650 | 4 | |a Pre-eclampsia |7 (dpeaa)DE-He213 | |
650 | 4 | |a DNA methylation |7 (dpeaa)DE-He213 | |
650 | 4 | |a Epigenetics |7 (dpeaa)DE-He213 | |
650 | 4 | |a Hypertensive disorder of pregnancy |7 (dpeaa)DE-He213 | |
650 | 4 | |a Surrogate variable analysis |7 (dpeaa)DE-He213 | |
700 | 1 | |a Fu, Haoyi |0 (orcid)0000-0003-2645-7239 |4 aut | |
700 | 1 | |a Ray, Mitali |0 (orcid)0000-0002-7175-8287 |4 aut | |
700 | 1 | |a Heinsberg, Lacey W. |0 (orcid)0000-0002-7690-5485 |4 aut | |
700 | 1 | |a Conley, Yvette P. |0 (orcid)0000-0002-1784-6067 |4 aut | |
700 | 1 | |a Anderson, Cindy M. |0 (orcid)0000-0002-8276-6557 |4 aut | |
700 | 1 | |a Hubel, Carl A. |0 (orcid)0000-0003-2326-9902 |4 aut | |
700 | 1 | |a Roberts, James M. |0 (orcid)0000-0002-2671-3207 |4 aut | |
700 | 1 | |a Jeyabalan, Arun |0 (orcid)0000-0002-8513-9663 |4 aut | |
700 | 1 | |a Weeks, Daniel E. |0 (orcid)0000-0001-9410-7228 |4 aut | |
700 | 1 | |a Schmella, Mandy J. |0 (orcid)0000-0003-3543-8048 |4 aut | |
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10.1186/s43682-022-00014-w doi (DE-627)SPR05138955X (SPR)s43682-022-00014-w-e DE-627 ger DE-627 rakwb eng Liu, Shuwei verfasserin (orcid)0000-0002-4089-8359 aut A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. Preeclampsia (dpeaa)DE-He213 Pre-eclampsia (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Hypertensive disorder of pregnancy (dpeaa)DE-He213 Surrogate variable analysis (dpeaa)DE-He213 Fu, Haoyi (orcid)0000-0003-2645-7239 aut Ray, Mitali (orcid)0000-0002-7175-8287 aut Heinsberg, Lacey W. (orcid)0000-0002-7690-5485 aut Conley, Yvette P. (orcid)0000-0002-1784-6067 aut Anderson, Cindy M. (orcid)0000-0002-8276-6557 aut Hubel, Carl A. (orcid)0000-0003-2326-9902 aut Roberts, James M. (orcid)0000-0002-2671-3207 aut Jeyabalan, Arun (orcid)0000-0002-8513-9663 aut Weeks, Daniel E. (orcid)0000-0001-9410-7228 aut Schmella, Mandy J. (orcid)0000-0003-3543-8048 aut Enthalten in Epigenetics Communications BioMed Central, 2021 3(2023), 1 vom: 26. Jan. (DE-627)1789629667 2730-7034 nnns volume:3 year:2023 number:1 day:26 month:01 https://dx.doi.org/10.1186/s43682-022-00014-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 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 3 2023 1 26 01 |
spelling |
10.1186/s43682-022-00014-w doi (DE-627)SPR05138955X (SPR)s43682-022-00014-w-e DE-627 ger DE-627 rakwb eng Liu, Shuwei verfasserin (orcid)0000-0002-4089-8359 aut A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. Preeclampsia (dpeaa)DE-He213 Pre-eclampsia (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Hypertensive disorder of pregnancy (dpeaa)DE-He213 Surrogate variable analysis (dpeaa)DE-He213 Fu, Haoyi (orcid)0000-0003-2645-7239 aut Ray, Mitali (orcid)0000-0002-7175-8287 aut Heinsberg, Lacey W. (orcid)0000-0002-7690-5485 aut Conley, Yvette P. (orcid)0000-0002-1784-6067 aut Anderson, Cindy M. (orcid)0000-0002-8276-6557 aut Hubel, Carl A. (orcid)0000-0003-2326-9902 aut Roberts, James M. (orcid)0000-0002-2671-3207 aut Jeyabalan, Arun (orcid)0000-0002-8513-9663 aut Weeks, Daniel E. (orcid)0000-0001-9410-7228 aut Schmella, Mandy J. (orcid)0000-0003-3543-8048 aut Enthalten in Epigenetics Communications BioMed Central, 2021 3(2023), 1 vom: 26. Jan. (DE-627)1789629667 2730-7034 nnns volume:3 year:2023 number:1 day:26 month:01 https://dx.doi.org/10.1186/s43682-022-00014-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 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 3 2023 1 26 01 |
allfields_unstemmed |
10.1186/s43682-022-00014-w doi (DE-627)SPR05138955X (SPR)s43682-022-00014-w-e DE-627 ger DE-627 rakwb eng Liu, Shuwei verfasserin (orcid)0000-0002-4089-8359 aut A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. Preeclampsia (dpeaa)DE-He213 Pre-eclampsia (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Hypertensive disorder of pregnancy (dpeaa)DE-He213 Surrogate variable analysis (dpeaa)DE-He213 Fu, Haoyi (orcid)0000-0003-2645-7239 aut Ray, Mitali (orcid)0000-0002-7175-8287 aut Heinsberg, Lacey W. (orcid)0000-0002-7690-5485 aut Conley, Yvette P. (orcid)0000-0002-1784-6067 aut Anderson, Cindy M. (orcid)0000-0002-8276-6557 aut Hubel, Carl A. (orcid)0000-0003-2326-9902 aut Roberts, James M. (orcid)0000-0002-2671-3207 aut Jeyabalan, Arun (orcid)0000-0002-8513-9663 aut Weeks, Daniel E. (orcid)0000-0001-9410-7228 aut Schmella, Mandy J. (orcid)0000-0003-3543-8048 aut Enthalten in Epigenetics Communications BioMed Central, 2021 3(2023), 1 vom: 26. Jan. (DE-627)1789629667 2730-7034 nnns volume:3 year:2023 number:1 day:26 month:01 https://dx.doi.org/10.1186/s43682-022-00014-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 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 3 2023 1 26 01 |
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10.1186/s43682-022-00014-w doi (DE-627)SPR05138955X (SPR)s43682-022-00014-w-e DE-627 ger DE-627 rakwb eng Liu, Shuwei verfasserin (orcid)0000-0002-4089-8359 aut A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. Preeclampsia (dpeaa)DE-He213 Pre-eclampsia (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Hypertensive disorder of pregnancy (dpeaa)DE-He213 Surrogate variable analysis (dpeaa)DE-He213 Fu, Haoyi (orcid)0000-0003-2645-7239 aut Ray, Mitali (orcid)0000-0002-7175-8287 aut Heinsberg, Lacey W. (orcid)0000-0002-7690-5485 aut Conley, Yvette P. (orcid)0000-0002-1784-6067 aut Anderson, Cindy M. (orcid)0000-0002-8276-6557 aut Hubel, Carl A. (orcid)0000-0003-2326-9902 aut Roberts, James M. (orcid)0000-0002-2671-3207 aut Jeyabalan, Arun (orcid)0000-0002-8513-9663 aut Weeks, Daniel E. (orcid)0000-0001-9410-7228 aut Schmella, Mandy J. (orcid)0000-0003-3543-8048 aut Enthalten in Epigenetics Communications BioMed Central, 2021 3(2023), 1 vom: 26. Jan. (DE-627)1789629667 2730-7034 nnns volume:3 year:2023 number:1 day:26 month:01 https://dx.doi.org/10.1186/s43682-022-00014-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 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 3 2023 1 26 01 |
allfieldsSound |
10.1186/s43682-022-00014-w doi (DE-627)SPR05138955X (SPR)s43682-022-00014-w-e DE-627 ger DE-627 rakwb eng Liu, Shuwei verfasserin (orcid)0000-0002-4089-8359 aut A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. Preeclampsia (dpeaa)DE-He213 Pre-eclampsia (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Hypertensive disorder of pregnancy (dpeaa)DE-He213 Surrogate variable analysis (dpeaa)DE-He213 Fu, Haoyi (orcid)0000-0003-2645-7239 aut Ray, Mitali (orcid)0000-0002-7175-8287 aut Heinsberg, Lacey W. (orcid)0000-0002-7690-5485 aut Conley, Yvette P. (orcid)0000-0002-1784-6067 aut Anderson, Cindy M. (orcid)0000-0002-8276-6557 aut Hubel, Carl A. (orcid)0000-0003-2326-9902 aut Roberts, James M. (orcid)0000-0002-2671-3207 aut Jeyabalan, Arun (orcid)0000-0002-8513-9663 aut Weeks, Daniel E. (orcid)0000-0001-9410-7228 aut Schmella, Mandy J. (orcid)0000-0003-3543-8048 aut Enthalten in Epigenetics Communications BioMed Central, 2021 3(2023), 1 vom: 26. Jan. (DE-627)1789629667 2730-7034 nnns volume:3 year:2023 number:1 day:26 month:01 https://dx.doi.org/10.1186/s43682-022-00014-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_187 GBV_ILN_213 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 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 3 2023 1 26 01 |
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Enthalten in Epigenetics Communications 3(2023), 1 vom: 26. Jan. volume:3 year:2023 number:1 day:26 month:01 |
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Preeclampsia Pre-eclampsia DNA methylation Epigenetics Hypertensive disorder of pregnancy Surrogate variable analysis |
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Liu, Shuwei @@aut@@ Fu, Haoyi @@aut@@ Ray, Mitali @@aut@@ Heinsberg, Lacey W. @@aut@@ Conley, Yvette P. @@aut@@ Anderson, Cindy M. @@aut@@ Hubel, Carl A. @@aut@@ Roberts, James M. @@aut@@ Jeyabalan, Arun @@aut@@ Weeks, Daniel E. @@aut@@ Schmella, Mandy J. @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR05138955X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230510061450.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230508s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s43682-022-00014-w</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR05138955X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s43682-022-00014-w-e</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="100" ind1="1" ind2=" "><subfield code="a">Liu, Shuwei</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-4089-8359</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="2"><subfield code="a">A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</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="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2023</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. 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Liu, Shuwei |
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Liu, Shuwei misc Preeclampsia misc Pre-eclampsia misc DNA methylation misc Epigenetics misc Hypertensive disorder of pregnancy misc Surrogate variable analysis A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy |
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A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy Preeclampsia (dpeaa)DE-He213 Pre-eclampsia (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Hypertensive disorder of pregnancy (dpeaa)DE-He213 Surrogate variable analysis (dpeaa)DE-He213 |
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misc Preeclampsia misc Pre-eclampsia misc DNA methylation misc Epigenetics misc Hypertensive disorder of pregnancy misc Surrogate variable analysis |
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A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy |
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Liu, Shuwei Fu, Haoyi Ray, Mitali Heinsberg, Lacey W. Conley, Yvette P. Anderson, Cindy M. Hubel, Carl A. Roberts, James M. Jeyabalan, Arun Weeks, Daniel E. Schmella, Mandy J. |
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title_sort |
longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy |
title_auth |
A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy |
abstract |
Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. © The Author(s) 2023 |
abstractGer |
Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. © The Author(s) 2023 |
abstract_unstemmed |
Background While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase. © The Author(s) 2023 |
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A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy |
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https://dx.doi.org/10.1186/s43682-022-00014-w |
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Fu, Haoyi Ray, Mitali Heinsberg, Lacey W. Conley, Yvette P. Anderson, Cindy M. Hubel, Carl A. Roberts, James M. Jeyabalan, Arun Weeks, Daniel E. Schmella, Mandy J. |
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Fu, Haoyi Ray, Mitali Heinsberg, Lacey W. Conley, Yvette P. Anderson, Cindy M. Hubel, Carl A. Roberts, James M. Jeyabalan, Arun Weeks, Daniel E. Schmella, Mandy J. |
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DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×$ 10^{-8} $, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×$ 10^{-5} $. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Preeclampsia</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pre-eclampsia</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA methylation</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenetics</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hypertensive disorder of pregnancy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Surrogate variable analysis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fu, Haoyi</subfield><subfield code="0">(orcid)0000-0003-2645-7239</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ray, Mitali</subfield><subfield code="0">(orcid)0000-0002-7175-8287</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Heinsberg, Lacey W.</subfield><subfield code="0">(orcid)0000-0002-7690-5485</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Conley, Yvette P.</subfield><subfield code="0">(orcid)0000-0002-1784-6067</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Anderson, Cindy M.</subfield><subfield code="0">(orcid)0000-0002-8276-6557</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hubel, Carl A.</subfield><subfield code="0">(orcid)0000-0003-2326-9902</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Roberts, James M.</subfield><subfield code="0">(orcid)0000-0002-2671-3207</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jeyabalan, Arun</subfield><subfield code="0">(orcid)0000-0002-8513-9663</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Weeks, Daniel E.</subfield><subfield code="0">(orcid)0000-0001-9410-7228</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Schmella, Mandy J.</subfield><subfield code="0">(orcid)0000-0003-3543-8048</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Epigenetics Communications</subfield><subfield code="d">BioMed Central, 2021</subfield><subfield code="g">3(2023), 1 vom: 26. 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score |
7.399638 |