Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation
Genome-wide association studies (GWAS) have identified multiple genetic loci for C-reactive protein (CRP) and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism. In...
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| Veröffentlicht in: | BMC genomics 2016-06, Vol.17 (1), p.443-443, Article 443 |
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| creator | Ligthart, Symen Vaez, Ahmad Hsu, Yi-Hsiang Stolk, Ronald Uitterlinden, André G Hofman, Albert Alizadeh, Behrooz Z Franco, Oscar H Dehghan, Abbas |
| description | Genome-wide association studies (GWAS) have identified multiple genetic loci for C-reactive protein (CRP) and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism.
In a bivariate GWAS, we combined summary statistics of published GWAS on CRP (n = 66,185) and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol (n = 100,184), using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB/FDFT1 (rs10435719, Preplication: 2.6 × 10(-5)), STAG1/PCCB (rs7621025, Preplication: 1.4 × 10(-3)) and FTO (rs1558902, Preplication: 2.7 × 10(-5)). Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB.
Our large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels. |
| doi_str_mv | 10.1186/s12864-016-2712-4 |
| format | Article |
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In a bivariate GWAS, we combined summary statistics of published GWAS on CRP (n = 66,185) and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol (n = 100,184), using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB/FDFT1 (rs10435719, Preplication: 2.6 × 10(-5)), STAG1/PCCB (rs7621025, Preplication: 1.4 × 10(-3)) and FTO (rs1558902, Preplication: 2.7 × 10(-5)). Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB.
Our large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels.</description><identifier>ISSN: 1471-2164</identifier><identifier>EISSN: 1471-2164</identifier><identifier>DOI: 10.1186/s12864-016-2712-4</identifier><identifier>PMID: 27286809</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Biomarkers ; C-Reactive Protein ; Cholesterol, HDL ; DNA Replication ; Gene Expression ; Genetic Association Studies ; Genome-wide association studies ; Genome-Wide Association Study ; Genomics ; Inflammation ; Inflammation - genetics ; Lipid metabolism ; Lipid Metabolism - genetics ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Triglycerides</subject><ispartof>BMC genomics, 2016-06, Vol.17 (1), p.443-443, Article 443</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>Ligthart et al. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-b1897017dff013f57364d7bd7427144fb199449929ef99ee318073e0b284b44b3</citedby><cites>FETCH-LOGICAL-c528t-b1897017dff013f57364d7bd7427144fb199449929ef99ee318073e0b284b44b3</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/PMC4901478/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901478/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27286809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ligthart, Symen</creatorcontrib><creatorcontrib>Vaez, Ahmad</creatorcontrib><creatorcontrib>Hsu, Yi-Hsiang</creatorcontrib><creatorcontrib>Stolk, Ronald</creatorcontrib><creatorcontrib>Uitterlinden, André G</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Alizadeh, Behrooz Z</creatorcontrib><creatorcontrib>Franco, Oscar H</creatorcontrib><creatorcontrib>Dehghan, Abbas</creatorcontrib><creatorcontrib>PMI-WG-XCP</creatorcontrib><creatorcontrib>LifeLines Cohort Study</creatorcontrib><creatorcontrib>Inflammation Working Group of the CHARGE Consortium</creatorcontrib><title>Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation</title><title>BMC genomics</title><addtitle>BMC Genomics</addtitle><description>Genome-wide association studies (GWAS) have identified multiple genetic loci for C-reactive protein (CRP) and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism.
In a bivariate GWAS, we combined summary statistics of published GWAS on CRP (n = 66,185) and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol (n = 100,184), using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB/FDFT1 (rs10435719, Preplication: 2.6 × 10(-5)), STAG1/PCCB (rs7621025, Preplication: 1.4 × 10(-3)) and FTO (rs1558902, Preplication: 2.7 × 10(-5)). Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB.
Our large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels.</description><subject>Analysis</subject><subject>Biomarkers</subject><subject>C-Reactive Protein</subject><subject>Cholesterol, HDL</subject><subject>DNA Replication</subject><subject>Gene Expression</subject><subject>Genetic Association Studies</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomics</subject><subject>Inflammation</subject><subject>Inflammation - genetics</subject><subject>Lipid metabolism</subject><subject>Lipid Metabolism - genetics</subject><subject>Multifactorial Inheritance</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Quantitative Trait Loci</subject><subject>Triglycerides</subject><issn>1471-2164</issn><issn>1471-2164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkk1vFSEUhidGY2v1B7gxJG50MRUYZoCNSW38aNLExI81YWYOVxoGRpi52n_vud5ae41hATk85-Xw5q2qp4yeMqa6V4Vx1Ymasq7mkvFa3KuOmZCs5qwT9--cj6pHpVxRyqTi7cPqiEtsVFQfV_DGb232dgGygZgmqH_4EYgtJQ1Y9SmSsqzjNcFqXLzzUEhMWwhkDuDTktPsBxIQJi5lEvzsx0JsHImPLthp-q3xuHrgbCjw5GY_qb6-e_vl_EN9-fH9xfnZZT20XC11z5SWOOToHGWNa2XTiVH2oxT4PSFcz7QWQmuuwWkN0DBFZQO050r0QvTNSfV6rzuv_QTjgCNnG8yc_WTztUnWm8Ob6L-ZTdoaoSmapVDgxY1ATt9XKIuZfBkgBBshrcUwqbtONbxtEX3-D3qV1hzxewbHopJSqsRfamMDGPQELbPDTtSciU4piY9KpE7_Q-EaYfJDiuA81g8aXh40ILPAz2Vj11LMxedPhyzbs0NOpWRwt34wanY5MvscGcyR2eXI7MZ-dtfI244_wWl-AUgiwkY</recordid><startdate>20160610</startdate><enddate>20160610</enddate><creator>Ligthart, Symen</creator><creator>Vaez, Ahmad</creator><creator>Hsu, Yi-Hsiang</creator><creator>Stolk, Ronald</creator><creator>Uitterlinden, André G</creator><creator>Hofman, Albert</creator><creator>Alizadeh, Behrooz Z</creator><creator>Franco, Oscar H</creator><creator>Dehghan, Abbas</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160610</creationdate><title>Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation</title><author>Ligthart, Symen ; Vaez, Ahmad ; Hsu, Yi-Hsiang ; Stolk, Ronald ; Uitterlinden, André G ; Hofman, Albert ; Alizadeh, Behrooz Z ; Franco, Oscar H ; Dehghan, Abbas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-b1897017dff013f57364d7bd7427144fb199449929ef99ee318073e0b284b44b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Biomarkers</topic><topic>C-Reactive Protein</topic><topic>Cholesterol, HDL</topic><topic>DNA Replication</topic><topic>Gene Expression</topic><topic>Genetic Association Studies</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomics</topic><topic>Inflammation</topic><topic>Inflammation - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ligthart, Symen</au><au>Vaez, Ahmad</au><au>Hsu, Yi-Hsiang</au><au>Stolk, Ronald</au><au>Uitterlinden, André G</au><au>Hofman, Albert</au><au>Alizadeh, Behrooz Z</au><au>Franco, Oscar H</au><au>Dehghan, Abbas</au><aucorp>PMI-WG-XCP</aucorp><aucorp>LifeLines Cohort Study</aucorp><aucorp>Inflammation Working Group of the CHARGE Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation</atitle><jtitle>BMC genomics</jtitle><addtitle>BMC Genomics</addtitle><date>2016-06-10</date><risdate>2016</risdate><volume>17</volume><issue>1</issue><spage>443</spage><epage>443</epage><pages>443-443</pages><artnum>443</artnum><issn>1471-2164</issn><eissn>1471-2164</eissn><abstract>Genome-wide association studies (GWAS) have identified multiple genetic loci for C-reactive protein (CRP) and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism.
In a bivariate GWAS, we combined summary statistics of published GWAS on CRP (n = 66,185) and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol (n = 100,184), using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB/FDFT1 (rs10435719, Preplication: 2.6 × 10(-5)), STAG1/PCCB (rs7621025, Preplication: 1.4 × 10(-3)) and FTO (rs1558902, Preplication: 2.7 × 10(-5)). Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB.
Our large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27286809</pmid><doi>10.1186/s12864-016-2712-4</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Biomarkers C-Reactive Protein Cholesterol, HDL DNA Replication Gene Expression Genetic Association Studies Genome-wide association studies Genome-Wide Association Study Genomics Inflammation Inflammation - genetics Lipid metabolism Lipid Metabolism - genetics Multifactorial Inheritance Polymorphism, Single Nucleotide Quantitative Trait Loci Triglycerides |
| title | Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation |
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