Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China

BACKGROUNDPreeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has...

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Published in:Hypertension in pregnancy 2023-12, Vol.42 (1), p.2256863-2256863
Main Authors: Cao, Zhenhua, Ma, Li, Cai, Wei, Niu, Xiulong, Yang, Ning, Ni, Jianmei, Wang, Xiaojing, Wei, Maoti, Chen, Shaobo, Li, Yuming
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genome-wide association study (gwas)
preeclampsia (pe)
single-nucleotide polymorphisms (snps)
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container_title Hypertension in pregnancy
container_volume 42
creator Cao, Zhenhua
Ma, Li
Cai, Wei
Niu, Xiulong
Yang, Ning
Ni, Jianmei
Wang, Xiaojing
Wei, Maoti
Chen, Shaobo
Li, Yuming
description BACKGROUNDPreeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. METHODThis study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. RESULTSIn the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P 
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Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. METHODThis study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. RESULTSIn the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P &lt; 10-5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P&lt;0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10-6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10-6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P &gt; 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P &lt; 0.000). CONCLUSIONIn this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.</description><identifier>ISSN: 1064-1955</identifier><identifier>EISSN: 1525-6065</identifier><identifier>DOI: 10.1080/10641955.2023.2256863</identifier><language>eng</language><publisher>Taylor &amp; Francis Group</publisher><subject>genome-wide association study (gwas) ; preeclampsia (pe) ; single-nucleotide polymorphisms (snps)</subject><ispartof>Hypertension in pregnancy, 2023-12, Vol.42 (1), p.2256863-2256863</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c347t-74e2979da73501c637eb8fa9a9a84cc9ce7fe64b4a112f4839919df3cd4f41283</cites><orcidid>0000-0001-5089-4303</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>Cao, Zhenhua</creatorcontrib><creatorcontrib>Ma, Li</creatorcontrib><creatorcontrib>Cai, Wei</creatorcontrib><creatorcontrib>Niu, Xiulong</creatorcontrib><creatorcontrib>Yang, Ning</creatorcontrib><creatorcontrib>Ni, Jianmei</creatorcontrib><creatorcontrib>Wang, Xiaojing</creatorcontrib><creatorcontrib>Wei, Maoti</creatorcontrib><creatorcontrib>Chen, Shaobo</creatorcontrib><creatorcontrib>Li, Yuming</creatorcontrib><title>Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China</title><title>Hypertension in pregnancy</title><description>BACKGROUNDPreeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. METHODThis study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. RESULTSIn the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P &lt; 10-5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P&lt;0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10-6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10-6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P &gt; 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P &lt; 0.000). CONCLUSIONIn this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.</description><subject>genome-wide association study (gwas)</subject><subject>preeclampsia (pe)</subject><subject>single-nucleotide polymorphisms (snps)</subject><issn>1064-1955</issn><issn>1525-6065</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpNkd2KFDEQhRtRcF19BCGXXmyP-e0f75bFnR1ZEXS8DtVJZc3QnbRJtzKv4tOacVaRuqhD8XEO1Kmq14xuGO3oW0YbyXqlNpxyseFcNV0jnlQXTHFVN7RRT4suTH2Cnlcvcj5Qylop1UX1a4shTlj_9BYJ5ByNh8XHQPKy2iNJ-ANhzOTuyy2_ItsP14xAsGT_efdRNIUnec0G58UPfvTLkTxgwExcTGROiGaEac4e3hEgJk7TGgpTD5DRkjnO6_h_lA9k7yEcfLgiN998gJfVM1ey8dXjvqy-3r7f39zV95-2u5vr-9oI2S51K5H3bW-hFYoy04gWh85BX6aTxvQGW4eNHCQwxp3sRN-z3jphrHSS8U5cVruzr41w0HPyE6SjjuD1n0NMDxrS4s2I2g2tZaw3VIKV7eDAccUEqqJEEbR4vTl7zSl-XzEvevLlQeMIAeOaNe-ajnEupCyoOqMmxZwTun_RjOpTr_pvr_rUq37sVfwGBymWrA</recordid><startdate>20231231</startdate><enddate>20231231</enddate><creator>Cao, Zhenhua</creator><creator>Ma, Li</creator><creator>Cai, Wei</creator><creator>Niu, Xiulong</creator><creator>Yang, Ning</creator><creator>Ni, Jianmei</creator><creator>Wang, Xiaojing</creator><creator>Wei, Maoti</creator><creator>Chen, Shaobo</creator><creator>Li, Yuming</creator><general>Taylor &amp; Francis Group</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5089-4303</orcidid></search><sort><creationdate>20231231</creationdate><title>Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China</title><author>Cao, Zhenhua ; Ma, Li ; Cai, Wei ; Niu, Xiulong ; Yang, Ning ; Ni, Jianmei ; Wang, Xiaojing ; Wei, Maoti ; Chen, Shaobo ; Li, Yuming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-74e2979da73501c637eb8fa9a9a84cc9ce7fe64b4a112f4839919df3cd4f41283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>genome-wide association study (gwas)</topic><topic>preeclampsia (pe)</topic><topic>single-nucleotide polymorphisms (snps)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Zhenhua</creatorcontrib><creatorcontrib>Ma, Li</creatorcontrib><creatorcontrib>Cai, Wei</creatorcontrib><creatorcontrib>Niu, Xiulong</creatorcontrib><creatorcontrib>Yang, Ning</creatorcontrib><creatorcontrib>Ni, Jianmei</creatorcontrib><creatorcontrib>Wang, Xiaojing</creatorcontrib><creatorcontrib>Wei, Maoti</creatorcontrib><creatorcontrib>Chen, Shaobo</creatorcontrib><creatorcontrib>Li, Yuming</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Hypertension in pregnancy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Zhenhua</au><au>Ma, Li</au><au>Cai, Wei</au><au>Niu, Xiulong</au><au>Yang, Ning</au><au>Ni, Jianmei</au><au>Wang, Xiaojing</au><au>Wei, Maoti</au><au>Chen, Shaobo</au><au>Li, Yuming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China</atitle><jtitle>Hypertension in pregnancy</jtitle><date>2023-12-31</date><risdate>2023</risdate><volume>42</volume><issue>1</issue><spage>2256863</spage><epage>2256863</epage><pages>2256863-2256863</pages><issn>1064-1955</issn><eissn>1525-6065</eissn><abstract>BACKGROUNDPreeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. METHODThis study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. RESULTSIn the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P &lt; 10-5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P&lt;0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10-6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10-6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P &gt; 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P &lt; 0.000). CONCLUSIONIn this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.</abstract><pub>Taylor &amp; Francis Group</pub><doi>10.1080/10641955.2023.2256863</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5089-4303</orcidid><oa>free_for_read</oa></addata></record>
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subjects genome-wide association study (gwas)
preeclampsia (pe)
single-nucleotide polymorphisms (snps)
title Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China
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