Genetic sharing with coronary artery disease identifies potential novel loci for bone mineral density
Bone mineral density (BMD) is a complex trait with high missing heritability. Numerous evidences have shown that BMD variation has a relationship with coronary artery disease (CAD). This relationship may come from a common genetic basis called pleiotropy. By leveraging the pleiotropy with CAD, we ma...
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| Veröffentlicht in: | Bone (New York, N.Y.) N.Y.), 2017-10, Vol.103, p.70-77 |
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| creator | Peng, Cheng Shen, Jie Lin, Xu Su, Kuan-Jui Greenbaum, Jonathan Zhu, Wei Lou, Hui-Ling Liu, Feng Zeng, Chun-Ping Deng, Wei-Feng Deng, Hong-Wen |
| description | Bone mineral density (BMD) is a complex trait with high missing heritability. Numerous evidences have shown that BMD variation has a relationship with coronary artery disease (CAD). This relationship may come from a common genetic basis called pleiotropy. By leveraging the pleiotropy with CAD, we may be able to improve the detection power of genetic variants associated with BMD. Using a recently developed conditional false discovery rate (cFDR) method, we jointly analyzed summary statistics from two large independent genome wide association studies (GWAS) of lumbar spine (LS) BMD and CAD. Strong pleiotropic enrichment and 7 pleiotropic SNPs were found for the two traits. We identified 41 SNPs for LS BMD (cFDR |
| doi_str_mv | 10.1016/j.bone.2017.06.016 |
| format | Article |
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•Applied cFDR method to GWAS data to identify potential novel SNPs for complex trait•Identified pleiotropic SNPs for BMD and coronary artery disease•Identified 21 potential novel loci for lumbar spine BMD</description><identifier>ISSN: 8756-3282</identifier><identifier>EISSN: 1873-2763</identifier><identifier>DOI: 10.1016/j.bone.2017.06.016</identifier><identifier>PMID: 28651948</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Bone Density - genetics ; Bone mineral density (BMD) ; Coronary artery disease (CAD) ; Coronary Artery Disease - genetics ; Genetic Pleiotropy - genetics ; Genetic Predisposition to Disease - genetics ; Genome wide association study (GWAS) ; Genome-Wide Association Study ; Humans ; Pleiotropy ; Polymorphism, Single Nucleotide</subject><ispartof>Bone (New York, N.Y.), 2017-10, Vol.103, p.70-77</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-9c80a65623bf6a299b0107bff26b3bd8e7792efc8b0decd95b33c39ff85514bb3</citedby><cites>FETCH-LOGICAL-c455t-9c80a65623bf6a299b0107bff26b3bd8e7792efc8b0decd95b33c39ff85514bb3</cites><orcidid>0000-0002-5163-9774</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S8756328217302156$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28651948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Cheng</creatorcontrib><creatorcontrib>Shen, Jie</creatorcontrib><creatorcontrib>Lin, Xu</creatorcontrib><creatorcontrib>Su, Kuan-Jui</creatorcontrib><creatorcontrib>Greenbaum, Jonathan</creatorcontrib><creatorcontrib>Zhu, Wei</creatorcontrib><creatorcontrib>Lou, Hui-Ling</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Zeng, Chun-Ping</creatorcontrib><creatorcontrib>Deng, Wei-Feng</creatorcontrib><creatorcontrib>Deng, Hong-Wen</creatorcontrib><title>Genetic sharing with coronary artery disease identifies potential novel loci for bone mineral density</title><title>Bone (New York, N.Y.)</title><addtitle>Bone</addtitle><description>Bone mineral density (BMD) is a complex trait with high missing heritability. Numerous evidences have shown that BMD variation has a relationship with coronary artery disease (CAD). This relationship may come from a common genetic basis called pleiotropy. By leveraging the pleiotropy with CAD, we may be able to improve the detection power of genetic variants associated with BMD. Using a recently developed conditional false discovery rate (cFDR) method, we jointly analyzed summary statistics from two large independent genome wide association studies (GWAS) of lumbar spine (LS) BMD and CAD. Strong pleiotropic enrichment and 7 pleiotropic SNPs were found for the two traits. We identified 41 SNPs for LS BMD (cFDR<0.05), of which 20 were replications of previous GWASs and 21 were potential novel SNPs that were not reported before. Four genes encompassed by 9 cFDR-significant SNPs were partially validated in the gene expression assay. Further functional enrichment analysis showed that genes corresponding to the cFDR-significant LS BMD SNPs were enriched in GO terms and KEGG pathways that played crucial roles in bone metabolism (adjP<0.05). In protein–protein interaction analysis, strong interactions were found between the proteins produced by the corresponding genes. Our study demonstrated the reliability and high-efficiency of the cFDR method on the detection of trait-associated genetic variants, the present findings shed novel insights into the genetic variability of BMD as well as the shared genetic basis underlying osteoporosis and CAD.
•Applied cFDR method to GWAS data to identify potential novel SNPs for complex trait•Identified pleiotropic SNPs for BMD and coronary artery disease•Identified 21 potential novel loci for lumbar spine BMD</description><subject>Bone Density - genetics</subject><subject>Bone mineral density (BMD)</subject><subject>Coronary artery disease (CAD)</subject><subject>Coronary Artery Disease - genetics</subject><subject>Genetic Pleiotropy - genetics</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome wide association study (GWAS)</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Pleiotropy</subject><subject>Polymorphism, Single Nucleotide</subject><issn>8756-3282</issn><issn>1873-2763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU2LFDEQDaK4s6t_wIPk6KXbfHS-QARZdBUWvOg5JOnKToaezpj0jOy_N83sLnrxVEXVq1ev6iH0hpKeEirf73qfZ-gZoaonsm-lZ2hDteIdU5I_RxuthOw40-wCXda6I4Rwo-hLdMG0FNQMeoPgBmZYUsB160qa7_DvtGxxyCXPrtxjVxZoYUwVXAWcRpiXFBNUfMjLmrsJz_kEE55ySDjmgldNeJ9mKK3X8DUt96_Qi-imCq8f4hX6-eXzj-uv3e33m2_Xn267MAixdCZo4qSQjPsoHTPGE0qUj5FJz_2oQSnDIAbtyQhhNMJzHriJUQtBB-_5Ffp45j0c_R7G0BQ2FfZQ0r5dY7NL9t_OnLb2Lp-sUEaKQTeCdw8EJf86Ql3sPtUA0-RmyMdqqaED08po0aDsDA0l11ogPq2hxK7-2J1df2FXfyyRtpXa0Nu_BT6NPBrSAB_OAGhvOiUotoYEc4AxFQiLHXP6H_8fjzWlZw</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Peng, Cheng</creator><creator>Shen, Jie</creator><creator>Lin, Xu</creator><creator>Su, Kuan-Jui</creator><creator>Greenbaum, Jonathan</creator><creator>Zhu, Wei</creator><creator>Lou, Hui-Ling</creator><creator>Liu, Feng</creator><creator>Zeng, Chun-Ping</creator><creator>Deng, Wei-Feng</creator><creator>Deng, Hong-Wen</creator><general>Elsevier Inc</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5163-9774</orcidid></search><sort><creationdate>20171001</creationdate><title>Genetic sharing with coronary artery disease identifies potential novel loci for bone mineral density</title><author>Peng, Cheng ; Shen, Jie ; Lin, Xu ; Su, Kuan-Jui ; Greenbaum, Jonathan ; Zhu, Wei ; Lou, Hui-Ling ; Liu, Feng ; Zeng, Chun-Ping ; Deng, Wei-Feng ; Deng, Hong-Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-9c80a65623bf6a299b0107bff26b3bd8e7792efc8b0decd95b33c39ff85514bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Bone Density - genetics</topic><topic>Bone mineral density (BMD)</topic><topic>Coronary artery disease (CAD)</topic><topic>Coronary Artery Disease - genetics</topic><topic>Genetic Pleiotropy - genetics</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genome wide association study (GWAS)</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Pleiotropy</topic><topic>Polymorphism, Single Nucleotide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Cheng</creatorcontrib><creatorcontrib>Shen, Jie</creatorcontrib><creatorcontrib>Lin, Xu</creatorcontrib><creatorcontrib>Su, Kuan-Jui</creatorcontrib><creatorcontrib>Greenbaum, Jonathan</creatorcontrib><creatorcontrib>Zhu, Wei</creatorcontrib><creatorcontrib>Lou, Hui-Ling</creatorcontrib><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Zeng, Chun-Ping</creatorcontrib><creatorcontrib>Deng, Wei-Feng</creatorcontrib><creatorcontrib>Deng, Hong-Wen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bone (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Cheng</au><au>Shen, Jie</au><au>Lin, Xu</au><au>Su, Kuan-Jui</au><au>Greenbaum, Jonathan</au><au>Zhu, Wei</au><au>Lou, Hui-Ling</au><au>Liu, Feng</au><au>Zeng, Chun-Ping</au><au>Deng, Wei-Feng</au><au>Deng, Hong-Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic sharing with coronary artery disease identifies potential novel loci for bone mineral density</atitle><jtitle>Bone (New York, N.Y.)</jtitle><addtitle>Bone</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>103</volume><spage>70</spage><epage>77</epage><pages>70-77</pages><issn>8756-3282</issn><eissn>1873-2763</eissn><abstract>Bone mineral density (BMD) is a complex trait with high missing heritability. Numerous evidences have shown that BMD variation has a relationship with coronary artery disease (CAD). This relationship may come from a common genetic basis called pleiotropy. By leveraging the pleiotropy with CAD, we may be able to improve the detection power of genetic variants associated with BMD. Using a recently developed conditional false discovery rate (cFDR) method, we jointly analyzed summary statistics from two large independent genome wide association studies (GWAS) of lumbar spine (LS) BMD and CAD. Strong pleiotropic enrichment and 7 pleiotropic SNPs were found for the two traits. We identified 41 SNPs for LS BMD (cFDR<0.05), of which 20 were replications of previous GWASs and 21 were potential novel SNPs that were not reported before. Four genes encompassed by 9 cFDR-significant SNPs were partially validated in the gene expression assay. Further functional enrichment analysis showed that genes corresponding to the cFDR-significant LS BMD SNPs were enriched in GO terms and KEGG pathways that played crucial roles in bone metabolism (adjP<0.05). In protein–protein interaction analysis, strong interactions were found between the proteins produced by the corresponding genes. Our study demonstrated the reliability and high-efficiency of the cFDR method on the detection of trait-associated genetic variants, the present findings shed novel insights into the genetic variability of BMD as well as the shared genetic basis underlying osteoporosis and CAD.
•Applied cFDR method to GWAS data to identify potential novel SNPs for complex trait•Identified pleiotropic SNPs for BMD and coronary artery disease•Identified 21 potential novel loci for lumbar spine BMD</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28651948</pmid><doi>10.1016/j.bone.2017.06.016</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5163-9774</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bone Density - genetics Bone mineral density (BMD) Coronary artery disease (CAD) Coronary Artery Disease - genetics Genetic Pleiotropy - genetics Genetic Predisposition to Disease - genetics Genome wide association study (GWAS) Genome-Wide Association Study Humans Pleiotropy Polymorphism, Single Nucleotide |
| title | Genetic sharing with coronary artery disease identifies potential novel loci for bone mineral density |
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