BMI-associated alleles do not constitute risk alleles for polycystic ovary syndrome independently of BMI: a case-control study
Polycystic Ovary Syndrome (PCOS) has a strong genetic background and the majority of patients with PCOS have elevated BMI levels. The aim of this study was to determine to which extent BMI-increasing alleles contribute to risk of PCOS when contemporaneous BMI is taken into consideration. Patients wi...
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| description | Polycystic Ovary Syndrome (PCOS) has a strong genetic background and the majority of patients with PCOS have elevated BMI levels. The aim of this study was to determine to which extent BMI-increasing alleles contribute to risk of PCOS when contemporaneous BMI is taken into consideration.
Patients with PCOS and controls were recruited from the United Kingdom (563 cases and 791 controls) and The Netherlands (510 cases and 2720 controls). Cases and controls were of similar BMI. SNPs mapping to 12 BMI-associated loci which have been extensively replicated across different ethnicities, i.e., BDNF, FAIM2, ETV5, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18, were studied in association with PCOS within each cohort using the additive genetic model followed by a combined analysis. A genetic allelic count risk score model was used to determine the risk of PCOS for individuals carrying increasing numbers of BMI-increasing alleles.
None of the genetic variants, including FTO and MC4R, was associated with PCOS independently of BMI in the meta-analysis. Moreover, no differences were observed between cases and controls in the number of BMI-risk alleles present and no overall trend across the risk score groups was observed.
In this combined analysis of over 4,000 BMI-matched individuals from the United Kingdom and the Netherlands, we observed no association of BMI risk alleles with PCOS independent of BMI. |
| doi_str_mv | 10.1371/journal.pone.0087335 |
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Patients with PCOS and controls were recruited from the United Kingdom (563 cases and 791 controls) and The Netherlands (510 cases and 2720 controls). Cases and controls were of similar BMI. SNPs mapping to 12 BMI-associated loci which have been extensively replicated across different ethnicities, i.e., BDNF, FAIM2, ETV5, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18, were studied in association with PCOS within each cohort using the additive genetic model followed by a combined analysis. A genetic allelic count risk score model was used to determine the risk of PCOS for individuals carrying increasing numbers of BMI-increasing alleles.
None of the genetic variants, including FTO and MC4R, was associated with PCOS independently of BMI in the meta-analysis. Moreover, no differences were observed between cases and controls in the number of BMI-risk alleles present and no overall trend across the risk score groups was observed.
In this combined analysis of over 4,000 BMI-matched individuals from the United Kingdom and the Netherlands, we observed no association of BMI risk alleles with PCOS independent of BMI.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0087335</identifier><identifier>PMID: 24498077</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alleles ; Bioinformatics ; Biology ; Body mass ; Body Mass Index ; Body Weight - genetics ; Brain-derived neurotrophic factor ; Case-Control Studies ; Consortia ; Diabetes ; Endocrinology ; Ethics ; Female ; Gene Frequency ; Gene mapping ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genetic variance ; Genetics ; Genomes ; Genotype ; Gynecology ; Humans ; Internal medicine ; Medical research ; Medicine ; Meta-analysis ; Metabolism ; Morphology ; Netherlands ; Obesity ; Obesity - genetics ; Obstetrics ; Overweight - genetics ; Patients ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - genetics ; Polymorphism, Single Nucleotide ; Population ; Reproductive health ; Risk ; Risk Assessment - methods ; Risk Assessment - statistics & numerical data ; Risk Factors ; Single-nucleotide polymorphism ; Studies ; Type 2 diabetes ; United Kingdom ; Womens health</subject><ispartof>PloS one, 2014-01, Vol.9 (1), p.e87335-e87335</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Louwers 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>2014 Louwers et al 2014 Louwers et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5683bd8ccda5df2fd9edb4ff2a4ddef141cb05df874b3f5925111f3d67e4cf6d3</citedby><cites>FETCH-LOGICAL-c692t-5683bd8ccda5df2fd9edb4ff2a4ddef141cb05df874b3f5925111f3d67e4cf6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909077/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909077/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24498077$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Randeva, Harpal Singh</contributor><creatorcontrib>Louwers, Yvonne V</creatorcontrib><creatorcontrib>Rayner, Nigel W</creatorcontrib><creatorcontrib>Herrera, Blanca M</creatorcontrib><creatorcontrib>Stolk, Lisette</creatorcontrib><creatorcontrib>Groves, Christopher J</creatorcontrib><creatorcontrib>Barber, Thomas M</creatorcontrib><creatorcontrib>Uitterlinden, Andre G</creatorcontrib><creatorcontrib>Franks, Stephen</creatorcontrib><creatorcontrib>Laven, Joop S E</creatorcontrib><creatorcontrib>McCarthy, Mark I</creatorcontrib><title>BMI-associated alleles do not constitute risk alleles for polycystic ovary syndrome independently of BMI: a case-control study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Polycystic Ovary Syndrome (PCOS) has a strong genetic background and the majority of patients with PCOS have elevated BMI levels. The aim of this study was to determine to which extent BMI-increasing alleles contribute to risk of PCOS when contemporaneous BMI is taken into consideration.
Patients with PCOS and controls were recruited from the United Kingdom (563 cases and 791 controls) and The Netherlands (510 cases and 2720 controls). Cases and controls were of similar BMI. SNPs mapping to 12 BMI-associated loci which have been extensively replicated across different ethnicities, i.e., BDNF, FAIM2, ETV5, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18, were studied in association with PCOS within each cohort using the additive genetic model followed by a combined analysis. A genetic allelic count risk score model was used to determine the risk of PCOS for individuals carrying increasing numbers of BMI-increasing alleles.
None of the genetic variants, including FTO and MC4R, was associated with PCOS independently of BMI in the meta-analysis. Moreover, no differences were observed between cases and controls in the number of BMI-risk alleles present and no overall trend across the risk score groups was observed.
In this combined analysis of over 4,000 BMI-matched individuals from the United Kingdom and the Netherlands, we observed no association of BMI risk alleles with PCOS independent of BMI.</description><subject>Alleles</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Body mass</subject><subject>Body Mass Index</subject><subject>Body Weight - genetics</subject><subject>Brain-derived neurotrophic factor</subject><subject>Case-Control Studies</subject><subject>Consortia</subject><subject>Diabetes</subject><subject>Endocrinology</subject><subject>Ethics</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Gene mapping</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic variance</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Internal medicine</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Meta-analysis</subject><subject>Metabolism</subject><subject>Morphology</subject><subject>Netherlands</subject><subject>Obesity</subject><subject>Obesity - genetics</subject><subject>Obstetrics</subject><subject>Overweight - genetics</subject><subject>Patients</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Reproductive health</subject><subject>Risk</subject><subject>Risk Assessment - methods</subject><subject>Risk Assessment - statistics & numerical data</subject><subject>Risk Factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Type 2 diabetes</subject><subject>United Kingdom</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNqNk1uL1DAUx4so7rr6DUQDguhDx6RJm3YfhHXxMrCy4O01pMnJTNdMMybpYl_87GZ2usOM7IMU2pDzO_9z68mypwTPCOXkzZUbfC_tbO16mGFcc0rLe9kxaWiRVwWm9_fOR9mjEK4wLmldVQ-zo4KxpsacH2d_3n2e5zIEpzoZQSNpLVgISDvUu4iU60Ps4hAB-S783JmN82jt7KjGZFbIXUs_ojD22rsVoK7XsIb06qMdkTMoBTlFEikZIE-S0TuLQhz0-Dh7YKQN8GT6nmTfP7z_dv4pv7j8OD8_u8hV1RQxL6uatrpWSstSm8LoBnTLjCkk0xoMYUS1OFlqzlpqyqYoCSGG6ooDU6bS9CR7vtVdWxfE1LogSMM5K3HBeSLmW0I7eSXWvlulkoSTnbi5cH4hpE-1WhCy5GUF0hBJNAPAbUqqlhxTDawtGSStt1O0oV2BVqkPXtoD0UNL3y3Fwl0L2uAG3yTzahLw7tcAIYpVFxRYK3twQ8qbNQ0pGCd1Ql_8g95d3UQtZCqg641LcdVGVJwxXte0wKxJ1OwOKj0aVl2aG5gu3R84vD5w2MwWfseFHEIQ869f_p-9_HHIvtxjlyBtXAZnh9il__EQZFtQeReCB7NrMsFisya33RCbNRHTmiS3Z_sD2jnd7gX9C2VqEMA</recordid><startdate>20140131</startdate><enddate>20140131</enddate><creator>Louwers, Yvonne V</creator><creator>Rayner, Nigel W</creator><creator>Herrera, Blanca M</creator><creator>Stolk, Lisette</creator><creator>Groves, Christopher J</creator><creator>Barber, Thomas M</creator><creator>Uitterlinden, Andre G</creator><creator>Franks, Stephen</creator><creator>Laven, Joop S E</creator><creator>McCarthy, Mark I</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140131</creationdate><title>BMI-associated alleles do not constitute risk alleles for polycystic ovary syndrome independently of BMI: a case-control study</title><author>Louwers, Yvonne V ; Rayner, Nigel W ; Herrera, Blanca M ; Stolk, Lisette ; Groves, Christopher J ; Barber, Thomas M ; Uitterlinden, Andre G ; Franks, Stephen ; Laven, Joop S E ; McCarthy, Mark I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5683bd8ccda5df2fd9edb4ff2a4ddef141cb05df874b3f5925111f3d67e4cf6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alleles</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Body mass</topic><topic>Body Mass Index</topic><topic>Body Weight - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Louwers, Yvonne V</au><au>Rayner, Nigel W</au><au>Herrera, Blanca M</au><au>Stolk, Lisette</au><au>Groves, Christopher J</au><au>Barber, Thomas M</au><au>Uitterlinden, Andre G</au><au>Franks, Stephen</au><au>Laven, Joop S E</au><au>McCarthy, Mark I</au><au>Randeva, Harpal Singh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BMI-associated alleles do not constitute risk alleles for polycystic ovary syndrome independently of BMI: a case-control study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-01-31</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>e87335</spage><epage>e87335</epage><pages>e87335-e87335</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Polycystic Ovary Syndrome (PCOS) has a strong genetic background and the majority of patients with PCOS have elevated BMI levels. The aim of this study was to determine to which extent BMI-increasing alleles contribute to risk of PCOS when contemporaneous BMI is taken into consideration.
Patients with PCOS and controls were recruited from the United Kingdom (563 cases and 791 controls) and The Netherlands (510 cases and 2720 controls). Cases and controls were of similar BMI. SNPs mapping to 12 BMI-associated loci which have been extensively replicated across different ethnicities, i.e., BDNF, FAIM2, ETV5, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18, were studied in association with PCOS within each cohort using the additive genetic model followed by a combined analysis. A genetic allelic count risk score model was used to determine the risk of PCOS for individuals carrying increasing numbers of BMI-increasing alleles.
None of the genetic variants, including FTO and MC4R, was associated with PCOS independently of BMI in the meta-analysis. Moreover, no differences were observed between cases and controls in the number of BMI-risk alleles present and no overall trend across the risk score groups was observed.
In this combined analysis of over 4,000 BMI-matched individuals from the United Kingdom and the Netherlands, we observed no association of BMI risk alleles with PCOS independent of BMI.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24498077</pmid><doi>10.1371/journal.pone.0087335</doi><tpages>e87335</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-01, Vol.9 (1), p.e87335-e87335 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1977450277 |
| 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 | Alleles Bioinformatics Biology Body mass Body Mass Index Body Weight - genetics Brain-derived neurotrophic factor Case-Control Studies Consortia Diabetes Endocrinology Ethics Female Gene Frequency Gene mapping Genetic diversity Genetic Predisposition to Disease - genetics Genetic variance Genetics Genomes Genotype Gynecology Humans Internal medicine Medical research Medicine Meta-analysis Metabolism Morphology Netherlands Obesity Obesity - genetics Obstetrics Overweight - genetics Patients Polycystic ovary syndrome Polycystic Ovary Syndrome - genetics Polymorphism, Single Nucleotide Population Reproductive health Risk Risk Assessment - methods Risk Assessment - statistics & numerical data Risk Factors Single-nucleotide polymorphism Studies Type 2 diabetes United Kingdom Womens health |
| title | BMI-associated alleles do not constitute risk alleles for polycystic ovary syndrome independently of BMI: a case-control study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T09%3A26%3A10IST&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=BMI-associated%20alleles%20do%20not%20constitute%20risk%20alleles%20for%20polycystic%20ovary%20syndrome%20independently%20of%20BMI:%20a%20case-control%20study&rft.jtitle=PloS%20one&rft.au=Louwers,%20Yvonne%20V&rft.date=2014-01-31&rft.volume=9&rft.issue=1&rft.spage=e87335&rft.epage=e87335&rft.pages=e87335-e87335&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0087335&rft_dat=%3Cgale_plos_%3EA478832049%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=1977450277&rft_id=info:pmid/24498077&rft_galeid=A478832049&rft_doaj_id=oai_doaj_org_article_a5756eaf1a1d4ee0ba5d8a703de4b54e&rfr_iscdi=true |