Integrating genome-wide association and eQTLs studies identifies the genes associated with age at menarche and age at natural menopause
An early onset of menarche and, later, menopause are well-established risk factors for the development of breast cancer and endometrial cancer. Although the largest GWASs have identified 389 independent signals for age at menarche (AAM) and 44 regions for age at menopause (ANM), GWAS can only identi...
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| creator | Wang, Gang Lv, Jian Qiu, Xiaoxin An, Yujun |
| description | An early onset of menarche and, later, menopause are well-established risk factors for the development of breast cancer and endometrial cancer. Although the largest GWASs have identified 389 independent signals for age at menarche (AAM) and 44 regions for age at menopause (ANM), GWAS can only identify the associations between variants and traits. The aim of this study was to identify genes whose expression levels were associated with AAM or ANM due to pleiotropy or causality by integrating GWAS data with genome-wide expression quantitative trait loci (eQTLs) data. We also aimed to identify the pleiotropic genes that influenced both phenotypes.
We employed GWAS data of AAM and ANM and genome-wide eQTL data from whole blood. The summary data-based Mendelian randomization method was used to prioritize the associated genes for further study. The colocalization analysis was used to identify the pleiotropic genes associated with both phenotypes.
We identified 31 genes whose expression was associated with AAM and 24 genes whose expression was associated with ANM due to pleiotropy or causality. Two pleiotropic genes were identified to be associated with both phenotypes.
The results point out the most possible genes which were responsible for the association. Our study prioritizes the associated genes for further functional mechanistic study of AAM and ANM and illustrates the benefit of integrating different omics data into the study of complex traits. |
| doi_str_mv | 10.1371/journal.pone.0213953 |
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We employed GWAS data of AAM and ANM and genome-wide eQTL data from whole blood. The summary data-based Mendelian randomization method was used to prioritize the associated genes for further study. The colocalization analysis was used to identify the pleiotropic genes associated with both phenotypes.
We identified 31 genes whose expression was associated with AAM and 24 genes whose expression was associated with ANM due to pleiotropy or causality. Two pleiotropic genes were identified to be associated with both phenotypes.
The results point out the most possible genes which were responsible for the association. Our study prioritizes the associated genes for further functional mechanistic study of AAM and ANM and illustrates the benefit of integrating different omics data into the study of complex traits.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0213953</identifier><identifier>PMID: 31206546</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Age ; Age Factors ; Biology and Life Sciences ; Breast cancer ; Cancer ; Cardiovascular disease ; Cell adhesion & migration ; Cell cycle ; Child ; Complications and side effects ; Consortia ; Datasets ; Dehydrogenases ; Deoxyribonucleic acid ; Diabetes ; DNA ; DNA repair ; Endocrinology ; Endometrial cancer ; Endometrium ; Female ; Gene expression ; Gene mapping ; Genes ; Genetic aspects ; Genetic Pleiotropy ; Genetics ; Genome-Wide Association Study - methods ; Genomes ; Genomics ; Gynecology ; Health risks ; Hospitals ; Humans ; Kinases ; Medical research ; Medicine and Health Sciences ; Menarche ; Menarche - genetics ; Menopause ; Menopause - genetics ; Meta-analysis ; Middle Aged ; Obstetrics ; Ovarian cancer ; Phenotype ; Phenotypes ; Physical Sciences ; Pleiotropy ; Quantitative genetics ; Quantitative Trait Loci ; Research and Analysis Methods ; Risk analysis ; Risk factors ; Studies ; Type 2 diabetes</subject><ispartof>PloS one, 2019-06, Vol.14 (6), p.e0213953-e0213953</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Wang et al 2019 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a96e2c51d838742d72cfd0f0c7d8923deb051da8d7b0edc29626509b8b5301353</citedby><cites>FETCH-LOGICAL-c692t-a96e2c51d838742d72cfd0f0c7d8923deb051da8d7b0edc29626509b8b5301353</cites><orcidid>0000-0002-5444-7313</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6576755/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6576755/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31206546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Glubb, Dylan</contributor><creatorcontrib>Wang, Gang</creatorcontrib><creatorcontrib>Lv, Jian</creatorcontrib><creatorcontrib>Qiu, Xiaoxin</creatorcontrib><creatorcontrib>An, Yujun</creatorcontrib><title>Integrating genome-wide association and eQTLs studies identifies the genes associated with age at menarche and age at natural menopause</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>An early onset of menarche and, later, menopause are well-established risk factors for the development of breast cancer and endometrial cancer. Although the largest GWASs have identified 389 independent signals for age at menarche (AAM) and 44 regions for age at menopause (ANM), GWAS can only identify the associations between variants and traits. The aim of this study was to identify genes whose expression levels were associated with AAM or ANM due to pleiotropy or causality by integrating GWAS data with genome-wide expression quantitative trait loci (eQTLs) data. We also aimed to identify the pleiotropic genes that influenced both phenotypes.
We employed GWAS data of AAM and ANM and genome-wide eQTL data from whole blood. The summary data-based Mendelian randomization method was used to prioritize the associated genes for further study. The colocalization analysis was used to identify the pleiotropic genes associated with both phenotypes.
We identified 31 genes whose expression was associated with AAM and 24 genes whose expression was associated with ANM due to pleiotropy or causality. Two pleiotropic genes were identified to be associated with both phenotypes.
The results point out the most possible genes which were responsible for the association. Our study prioritizes the associated genes for further functional mechanistic study of AAM and ANM and illustrates the benefit of integrating different omics data into the study of complex traits.</description><subject>Adolescent</subject><subject>Age</subject><subject>Age Factors</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cardiovascular disease</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Child</subject><subject>Complications and side effects</subject><subject>Consortia</subject><subject>Datasets</subject><subject>Dehydrogenases</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>DNA</subject><subject>DNA repair</subject><subject>Endocrinology</subject><subject>Endometrial cancer</subject><subject>Endometrium</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Pleiotropy</subject><subject>Genetics</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Gynecology</subject><subject>Health risks</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Menarche</subject><subject>Menarche - genetics</subject><subject>Menopause</subject><subject>Menopause - genetics</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Obstetrics</subject><subject>Ovarian cancer</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Physical Sciences</subject><subject>Pleiotropy</subject><subject>Quantitative genetics</subject><subject>Quantitative Trait Loci</subject><subject>Research and Analysis Methods</subject><subject>Risk 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diabetes</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk81u1DAQxyMEoqXwBggiISE47OKP2EkuSFXFx0orVUDhajn2JOtVYi-xQ9sn4LVx2Gy1QT2gHDKa-c3fM2NPkjzHaIlpjt9t3dBb2S53zsISEUxLRh8kp7ikZMEJog-P7JPkifdbhBgtOH-cnFBMEGcZP01-r2yAppfB2CZtwLoOFtdGQyq9d8pEv7OptDqFL1drn_owaAM-jYQNph7NsIExMVqHFNDptQmbVDZRJqQdWNmrSI0yk8_KMPSyHWNuJwcPT5NHtWw9PJv-Z8n3jx-uLj4v1pefVhfn64XiJQkLWXIgimFd0CLPiM6JqjWqkcp1URKqoUIxKAudVwi0IiUnnKGyKipGEaaMniUv97q71nkxzdALQjKCESVlGYnVntBObsWuN53sb4WTRvx1uL4Rsg9GtSDyAuMqUzUiOctyXsga1RpzhgkhZcVp1Ho_nTZUXawnDi12PROdR6zZiMb9EpzlPGdjuW8mgd79HMAH0RmvoG2lBTfs6y4oRiSL6Kt_0Pu7m6hGxgaMrV08V42i4pwVZcazrBjrXt5DxU9DZ1R8cLWJ_lnC21lCZALchCZerRerb1__n738MWdfH7EbkG3YeNcO47P0czDbg6p33vdQ3w0ZIzHuy2EaYtwXMe1LTHtxfEF3SYcFoX8A8AsQkA</recordid><startdate>20190617</startdate><enddate>20190617</enddate><creator>Wang, 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genome-wide association and eQTLs studies identifies the genes associated with age at menarche and age at natural menopause</title><author>Wang, Gang ; Lv, Jian ; Qiu, Xiaoxin ; An, Yujun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a96e2c51d838742d72cfd0f0c7d8923deb051da8d7b0edc29626509b8b5301353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Age</topic><topic>Age Factors</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cardiovascular disease</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Child</topic><topic>Complications and side effects</topic><topic>Consortia</topic><topic>Datasets</topic><topic>Dehydrogenases</topic><topic>Deoxyribonucleic acid</topic><topic>Diabetes</topic><topic>DNA</topic><topic>DNA repair</topic><topic>Endocrinology</topic><topic>Endometrial cancer</topic><topic>Endometrium</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene mapping</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Pleiotropy</topic><topic>Genetics</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Gynecology</topic><topic>Health risks</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Menarche</topic><topic>Menarche - genetics</topic><topic>Menopause</topic><topic>Menopause - genetics</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Obstetrics</topic><topic>Ovarian cancer</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Physical Sciences</topic><topic>Pleiotropy</topic><topic>Quantitative genetics</topic><topic>Quantitative Trait Loci</topic><topic>Research and Analysis Methods</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Studies</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Gang</creatorcontrib><creatorcontrib>Lv, Jian</creatorcontrib><creatorcontrib>Qiu, Xiaoxin</creatorcontrib><creatorcontrib>An, Yujun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health 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Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Gang</au><au>Lv, Jian</au><au>Qiu, Xiaoxin</au><au>An, Yujun</au><au>Glubb, Dylan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrating genome-wide association and eQTLs studies identifies the genes associated with age at menarche and age at natural menopause</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-06-17</date><risdate>2019</risdate><volume>14</volume><issue>6</issue><spage>e0213953</spage><epage>e0213953</epage><pages>e0213953-e0213953</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>An early onset of menarche and, later, menopause are well-established risk factors for the development of breast cancer and endometrial cancer. Although the largest GWASs have identified 389 independent signals for age at menarche (AAM) and 44 regions for age at menopause (ANM), GWAS can only identify the associations between variants and traits. The aim of this study was to identify genes whose expression levels were associated with AAM or ANM due to pleiotropy or causality by integrating GWAS data with genome-wide expression quantitative trait loci (eQTLs) data. We also aimed to identify the pleiotropic genes that influenced both phenotypes.
We employed GWAS data of AAM and ANM and genome-wide eQTL data from whole blood. The summary data-based Mendelian randomization method was used to prioritize the associated genes for further study. The colocalization analysis was used to identify the pleiotropic genes associated with both phenotypes.
We identified 31 genes whose expression was associated with AAM and 24 genes whose expression was associated with ANM due to pleiotropy or causality. Two pleiotropic genes were identified to be associated with both phenotypes.
The results point out the most possible genes which were responsible for the association. Our study prioritizes the associated genes for further functional mechanistic study of AAM and ANM and illustrates the benefit of integrating different omics data into the study of complex traits.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31206546</pmid><doi>10.1371/journal.pone.0213953</doi><tpages>e0213953</tpages><orcidid>https://orcid.org/0000-0002-5444-7313</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Age Age Factors Biology and Life Sciences Breast cancer Cancer Cardiovascular disease Cell adhesion & migration Cell cycle Child Complications and side effects Consortia Datasets Dehydrogenases Deoxyribonucleic acid Diabetes DNA DNA repair Endocrinology Endometrial cancer Endometrium Female Gene expression Gene mapping Genes Genetic aspects Genetic Pleiotropy Genetics Genome-Wide Association Study - methods Genomes Genomics Gynecology Health risks Hospitals Humans Kinases Medical research Medicine and Health Sciences Menarche Menarche - genetics Menopause Menopause - genetics Meta-analysis Middle Aged Obstetrics Ovarian cancer Phenotype Phenotypes Physical Sciences Pleiotropy Quantitative genetics Quantitative Trait Loci Research and Analysis Methods Risk analysis Risk factors Studies Type 2 diabetes |
| title | Integrating genome-wide association and eQTLs studies identifies the genes associated with age at menarche and age at natural menopause |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T20%3A57%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Integrating%20genome-wide%20association%20and%20eQTLs%20studies%20identifies%20the%20genes%20associated%20with%20age%20at%20menarche%20and%20age%20at%20natural%20menopause&rft.jtitle=PloS%20one&rft.au=Wang,%20Gang&rft.date=2019-06-17&rft.volume=14&rft.issue=6&rft.spage=e0213953&rft.epage=e0213953&rft.pages=e0213953-e0213953&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0213953&rft_dat=%3Cgale_plos_%3EA589464483%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2242103299&rft_id=info:pmid/31206546&rft_galeid=A589464483&rft_doaj_id=oai_doaj_org_article_7811b4cf02754768af0fd16512229b63&rfr_iscdi=true |