Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer
Epidemiological and clinical evidences have shown that bone mineral density (BMD) has a close relationship with breast cancer (BC). They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects, we may be able to explore more of the traits’ total he...
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| Veröffentlicht in: | Calcified tissue international 2017-11, Vol.101 (5), p.489-500 |
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| creator | Peng, Cheng Lou, Hui-Ling Liu, Feng Shen, Jie Lin, Xu Zeng, Chun-Ping Long, Ji-Rong Su, Kuan-Jui Zhang, Lan Greenbaum, Jonathan Deng, Wei-Feng Li, Yu-Mei Deng, Hong-Wen |
| description | Epidemiological and clinical evidences have shown that bone mineral density (BMD) has a close relationship with breast cancer (BC). They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects, we may be able to explore more of the traits’ total heritability. We applied a recently developed conditional false discovery rate (cFDR) method to the summary statistics from two independent GWASs to identify the potential pleiotropic genetic variants for BMD and BC. By jointly analyzing two large independent GWASs of BMD and BC, we found strong pleiotropic enrichment between them and identified 102 single-nucleotide polymorphisms (SNPs) in BMD and 192 SNPs in BC with cFDR |
| doi_str_mv | 10.1007/s00223-017-0308-x |
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They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects, we may be able to explore more of the traits’ total heritability. We applied a recently developed conditional false discovery rate (cFDR) method to the summary statistics from two independent GWASs to identify the potential pleiotropic genetic variants for BMD and BC. By jointly analyzing two large independent GWASs of BMD and BC, we found strong pleiotropic enrichment between them and identified 102 single-nucleotide polymorphisms (SNPs) in BMD and 192 SNPs in BC with cFDR < 0.05, including 230 SNPs that might have been overlooked by the standard GWAS analysis. cFDR-significant genes were enriched in GO terms and KEGG pathways which were crucial to bone metabolism and/or BC pathology (adjP < 0.05). Some cFDR-significant genes were partially validated in the gene expressional validation assay. Strong interactions were found between proteins produced by cFDR-significant genes in the context of biological mechanism of bone metabolism and/or BC etiology. Totally, we identified 7 pleiotropic SNPs that were associated with both BMD and BC (conjunction cFDR < 0.05); CCDC170, ESR1, RANKL, CPED1, and MEOX1 might play important roles in the pleiotropy of BMD and BC. Our study highlighted the significant pleiotropy between BMD and BC and shed novel insight into trait-specific as well as the potentially shared genetic architecture for both BMD and BC.</description><identifier>ISSN: 0171-967X</identifier><identifier>EISSN: 1432-0827</identifier><identifier>DOI: 10.1007/s00223-017-0308-x</identifier><identifier>PMID: 28761973</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Bone cancer ; Bone density ; Bone mineral density ; Bone turnover ; Breast cancer ; Cell Biology ; Endocrinology ; ESR1 protein ; Etiology ; Genetic diversity ; Heritability ; Life Sciences ; Metabolism ; Original Research ; Orthopedics ; Pleiotropy ; Single-nucleotide polymorphism ; Statistical analysis ; TRANCE protein</subject><ispartof>Calcified tissue international, 2017-11, Vol.101 (5), p.489-500</ispartof><rights>Springer Science+Business Media, LLC 2017</rights><rights>Calcified Tissue International is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-b2910ffa338b2d38a5efada80100b792dca014d60ae78398aff0d134a1d1ccb23</citedby><cites>FETCH-LOGICAL-c470t-b2910ffa338b2d38a5efada80100b792dca014d60ae78398aff0d134a1d1ccb23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00223-017-0308-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00223-017-0308-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28761973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Cheng</creatorcontrib><creatorcontrib>Lou, Hui-Ling</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Shen, Jie</creatorcontrib><creatorcontrib>Lin, Xu</creatorcontrib><creatorcontrib>Zeng, Chun-Ping</creatorcontrib><creatorcontrib>Long, Ji-Rong</creatorcontrib><creatorcontrib>Su, Kuan-Jui</creatorcontrib><creatorcontrib>Zhang, Lan</creatorcontrib><creatorcontrib>Greenbaum, Jonathan</creatorcontrib><creatorcontrib>Deng, Wei-Feng</creatorcontrib><creatorcontrib>Li, Yu-Mei</creatorcontrib><creatorcontrib>Deng, Hong-Wen</creatorcontrib><title>Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer</title><title>Calcified tissue international</title><addtitle>Calcif Tissue Int</addtitle><addtitle>Calcif Tissue Int</addtitle><description>Epidemiological and clinical evidences have shown that bone mineral density (BMD) has a close relationship with breast cancer (BC). They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects, we may be able to explore more of the traits’ total heritability. We applied a recently developed conditional false discovery rate (cFDR) method to the summary statistics from two independent GWASs to identify the potential pleiotropic genetic variants for BMD and BC. By jointly analyzing two large independent GWASs of BMD and BC, we found strong pleiotropic enrichment between them and identified 102 single-nucleotide polymorphisms (SNPs) in BMD and 192 SNPs in BC with cFDR < 0.05, including 230 SNPs that might have been overlooked by the standard GWAS analysis. cFDR-significant genes were enriched in GO terms and KEGG pathways which were crucial to bone metabolism and/or BC pathology (adjP < 0.05). Some cFDR-significant genes were partially validated in the gene expressional validation assay. Strong interactions were found between proteins produced by cFDR-significant genes in the context of biological mechanism of bone metabolism and/or BC etiology. Totally, we identified 7 pleiotropic SNPs that were associated with both BMD and BC (conjunction cFDR < 0.05); CCDC170, ESR1, RANKL, CPED1, and MEOX1 might play important roles in the pleiotropy of BMD and BC. Our study highlighted the significant pleiotropy between BMD and BC and shed novel insight into trait-specific as well as the potentially shared genetic architecture for both BMD and BC.</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Bone cancer</subject><subject>Bone density</subject><subject>Bone mineral density</subject><subject>Bone turnover</subject><subject>Breast cancer</subject><subject>Cell Biology</subject><subject>Endocrinology</subject><subject>ESR1 protein</subject><subject>Etiology</subject><subject>Genetic diversity</subject><subject>Heritability</subject><subject>Life Sciences</subject><subject>Metabolism</subject><subject>Original Research</subject><subject>Orthopedics</subject><subject>Pleiotropy</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>TRANCE protein</subject><issn>0171-967X</issn><issn>1432-0827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1rVTEQhoMo9lr9AW4k4MbN0Xyck-RsBHuttVCxCxV3YU4-2pRzk9skV9p_bw63liq4Gph55p15eRF6SclbSoh8VwhhjHeEyo5worqbR2hFe846oph8jFZtQLtRyJ8H6FkpV4TQXgjxFB0wJQUdJV-h-TheQjTO4lPrYg0-GKghRZw8Pk91acGMz2cXUs1pGww-cdHVVn9ADhBrwT5lfJSiw19CdLnRH10sod5iiBYfZQel4vVyIz9HTzzMxb24q4fo-6fjb-vP3dnXk9P1h7PO9JLUbmIjJd4D52pilisYnAcLijTTkxyZNdCcWEHAScVHBd4TS3kP1FJjJsYP0fu97nY3bZw1zUX7S29z2EC-1QmC_nsSw6W-SL_0IEcx9KIJvLkTyOl650rVm1CMm2eILu2KpiMbmFJULejrf9CrtMux2WvUQBmTUvBG0T1lciolO3__DCV6yVLvs9QtMr1kqW_azquHLu43_oTXALYHShvFC5cfnP6v6m-5GaxR</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Peng, Cheng</creator><creator>Lou, Hui-Ling</creator><creator>Liu, Feng</creator><creator>Shen, Jie</creator><creator>Lin, Xu</creator><creator>Zeng, Chun-Ping</creator><creator>Long, Ji-Rong</creator><creator>Su, Kuan-Jui</creator><creator>Zhang, Lan</creator><creator>Greenbaum, Jonathan</creator><creator>Deng, Wei-Feng</creator><creator>Li, Yu-Mei</creator><creator>Deng, Hong-Wen</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171101</creationdate><title>Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer</title><author>Peng, Cheng ; Lou, Hui-Ling ; Liu, Feng ; Shen, Jie ; Lin, Xu ; Zeng, Chun-Ping ; Long, Ji-Rong ; Su, Kuan-Jui ; Zhang, Lan ; Greenbaum, Jonathan ; Deng, Wei-Feng ; Li, Yu-Mei ; Deng, Hong-Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-b2910ffa338b2d38a5efada80100b792dca014d60ae78398aff0d134a1d1ccb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Bone cancer</topic><topic>Bone density</topic><topic>Bone mineral density</topic><topic>Bone turnover</topic><topic>Breast cancer</topic><topic>Cell Biology</topic><topic>Endocrinology</topic><topic>ESR1 protein</topic><topic>Etiology</topic><topic>Genetic diversity</topic><topic>Heritability</topic><topic>Life Sciences</topic><topic>Metabolism</topic><topic>Original Research</topic><topic>Orthopedics</topic><topic>Pleiotropy</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>TRANCE protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Cheng</creatorcontrib><creatorcontrib>Lou, Hui-Ling</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Shen, Jie</creatorcontrib><creatorcontrib>Lin, Xu</creatorcontrib><creatorcontrib>Zeng, Chun-Ping</creatorcontrib><creatorcontrib>Long, Ji-Rong</creatorcontrib><creatorcontrib>Su, Kuan-Jui</creatorcontrib><creatorcontrib>Zhang, Lan</creatorcontrib><creatorcontrib>Greenbaum, Jonathan</creatorcontrib><creatorcontrib>Deng, Wei-Feng</creatorcontrib><creatorcontrib>Li, Yu-Mei</creatorcontrib><creatorcontrib>Deng, Hong-Wen</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Calcified tissue international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Cheng</au><au>Lou, Hui-Ling</au><au>Liu, Feng</au><au>Shen, Jie</au><au>Lin, Xu</au><au>Zeng, Chun-Ping</au><au>Long, Ji-Rong</au><au>Su, Kuan-Jui</au><au>Zhang, Lan</au><au>Greenbaum, Jonathan</au><au>Deng, Wei-Feng</au><au>Li, Yu-Mei</au><au>Deng, Hong-Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer</atitle><jtitle>Calcified tissue international</jtitle><stitle>Calcif Tissue Int</stitle><addtitle>Calcif Tissue Int</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>101</volume><issue>5</issue><spage>489</spage><epage>500</epage><pages>489-500</pages><issn>0171-967X</issn><eissn>1432-0827</eissn><abstract>Epidemiological and clinical evidences have shown that bone mineral density (BMD) has a close relationship with breast cancer (BC). They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects, we may be able to explore more of the traits’ total heritability. We applied a recently developed conditional false discovery rate (cFDR) method to the summary statistics from two independent GWASs to identify the potential pleiotropic genetic variants for BMD and BC. By jointly analyzing two large independent GWASs of BMD and BC, we found strong pleiotropic enrichment between them and identified 102 single-nucleotide polymorphisms (SNPs) in BMD and 192 SNPs in BC with cFDR < 0.05, including 230 SNPs that might have been overlooked by the standard GWAS analysis. cFDR-significant genes were enriched in GO terms and KEGG pathways which were crucial to bone metabolism and/or BC pathology (adjP < 0.05). Some cFDR-significant genes were partially validated in the gene expressional validation assay. Strong interactions were found between proteins produced by cFDR-significant genes in the context of biological mechanism of bone metabolism and/or BC etiology. Totally, we identified 7 pleiotropic SNPs that were associated with both BMD and BC (conjunction cFDR < 0.05); CCDC170, ESR1, RANKL, CPED1, and MEOX1 might play important roles in the pleiotropy of BMD and BC. Our study highlighted the significant pleiotropy between BMD and BC and shed novel insight into trait-specific as well as the potentially shared genetic architecture for both BMD and BC.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28761973</pmid><doi>10.1007/s00223-017-0308-x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biochemistry Biomedical and Life Sciences Bone cancer Bone density Bone mineral density Bone turnover Breast cancer Cell Biology Endocrinology ESR1 protein Etiology Genetic diversity Heritability Life Sciences Metabolism Original Research Orthopedics Pleiotropy Single-nucleotide polymorphism Statistical analysis TRANCE protein |
| title | Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer |
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