Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study
Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart St...
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| Veröffentlicht in: | Journal of human genetics 2015-12, Vol.60 (12), p.755-761 |
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| creator | Li, Jin Lange, Leslie A Sabourin, Jeremy Duan, Qing Valdar, William Willis, Monte S Li, Yun Wilson, James G Lange, Ethan M |
| description | Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P |
| doi_str_mv | 10.1038/jhg.2015.107 |
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Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P<5 × 10(-8)) after adjusting for the local ancestry at 6q25.3. Interestingly, before adjusting for local ancestry, we observed significant (P<5 × 10(-8)) associations for hundreds of SNPs spanning ~10 Mb region on 6q surrounding the LPA gene, whereas after adjusting for local ancestry, the region containing significantly associated SNPs got much narrower and was centered over the LPA gene (<1 Mb). We observed a single nonsynonymous SNP in APOE significantly associated with Lp(a) (P<5 × 10(-8)). A high burden of coding variants in LPA and APOE were also associated with higher Lp(a) levels. Our study provides evidence that ancestry-specific causal risk variant(s) resides in or near LPA and that most of the observed associations outside this narrower region are spurious associations.</description><identifier>ISSN: 1434-5161</identifier><identifier>EISSN: 1435-232X</identifier><identifier>DOI: 10.1038/jhg.2015.107</identifier><identifier>PMID: 26377243</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>African Americans ; Age ; Apolipoprotein E ; Apolipoproteins ; Apolipoproteins E - genetics ; Body mass index ; Cardiovascular diseases ; Cardiovascular Diseases - genetics ; Chromosome 6 ; Chromosomes, Human, Pair 6 - genetics ; European Continental Ancestry Group ; Female ; Genetics ; Genome-Wide Association Study ; Genomes ; Genotype & phenotype ; Heart ; Humans ; Lipoprotein(a) - genetics ; Lipoproteins ; Male ; Mississippi ; Polymorphism, Single Nucleotide ; Risk factors ; Single-nucleotide polymorphism ; Studies</subject><ispartof>Journal of human genetics, 2015-12, Vol.60 (12), p.755-761</ispartof><rights>Copyright Nature Publishing Group Dec 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-7a605cab66637a69e0e25015e7a11f3c8dc65109770a36f3941da97cb72b41ca3</citedby><cites>FETCH-LOGICAL-c469t-7a605cab66637a69e0e25015e7a11f3c8dc65109770a36f3941da97cb72b41ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26377243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Jin</creatorcontrib><creatorcontrib>Lange, Leslie A</creatorcontrib><creatorcontrib>Sabourin, Jeremy</creatorcontrib><creatorcontrib>Duan, Qing</creatorcontrib><creatorcontrib>Valdar, William</creatorcontrib><creatorcontrib>Willis, Monte S</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Wilson, James G</creatorcontrib><creatorcontrib>Lange, Ethan M</creatorcontrib><title>Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study</title><title>Journal of human genetics</title><addtitle>J Hum Genet</addtitle><description>Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P<5 × 10(-8)) after adjusting for the local ancestry at 6q25.3. Interestingly, before adjusting for local ancestry, we observed significant (P<5 × 10(-8)) associations for hundreds of SNPs spanning ~10 Mb region on 6q surrounding the LPA gene, whereas after adjusting for local ancestry, the region containing significantly associated SNPs got much narrower and was centered over the LPA gene (<1 Mb). We observed a single nonsynonymous SNP in APOE significantly associated with Lp(a) (P<5 × 10(-8)). A high burden of coding variants in LPA and APOE were also associated with higher Lp(a) levels. Our study provides evidence that ancestry-specific causal risk variant(s) resides in or near LPA and that most of the observed associations outside this narrower region are spurious associations.</description><subject>African Americans</subject><subject>Age</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins E - genetics</subject><subject>Body mass index</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Chromosome 6</subject><subject>Chromosomes, Human, Pair 6 - genetics</subject><subject>European Continental Ancestry Group</subject><subject>Female</subject><subject>Genetics</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Heart</subject><subject>Humans</subject><subject>Lipoprotein(a) - genetics</subject><subject>Lipoproteins</subject><subject>Male</subject><subject>Mississippi</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><issn>1434-5161</issn><issn>1435-232X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkc1LxDAQxYMoft88S8DLClYzSZq0RxHdVQQPKngQSppOteu2WZsW9b83dVcPHsTTm4HfPN7wCNkDdgxMJCfT56djziAOm14hmyBFHHHBH1a_ZhnFoGCDbHk_ZYwJrvk62eBKaM2l2CSPY2xcjRE1TUHxfRjfqgKp8d7ZynSVa6jv-uKDupJ6bPuazqq5m7euw6qhI3NIg3TPSK-MffGBnqBpO3o73OyQtdLMPO4udZvcX5zfnU2i65vx5dnpdWSlSrtIG8Via3KlQiyjUmTI4_ARagNQCpsUVsXAUq2ZEaoUqYTCpNrmmucSrBHbZLTwDbFee_RdVlfe4mxmGnS9z0CrONWplvAPNGZSiCRVAT34hU5d3zbhkYwLAYprBslfFCRSap6E5IE6WlC2dd63WGbztqpN-5EBy4Yas1BjNtQYNh3w_aVpn9dY_MDfvYlPZQiVGw</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Li, Jin</creator><creator>Lange, Leslie A</creator><creator>Sabourin, Jeremy</creator><creator>Duan, Qing</creator><creator>Valdar, William</creator><creator>Willis, Monte S</creator><creator>Li, Yun</creator><creator>Wilson, James G</creator><creator>Lange, Ethan M</creator><general>Nature Publishing Group</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</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>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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20151201</creationdate><title>Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study</title><author>Li, Jin ; Lange, Leslie A ; Sabourin, Jeremy ; Duan, Qing ; Valdar, William ; Willis, Monte S ; Li, Yun ; Wilson, James G ; Lange, Ethan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-7a605cab66637a69e0e25015e7a11f3c8dc65109770a36f3941da97cb72b41ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>African Americans</topic><topic>Age</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins E - genetics</topic><topic>Body mass index</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Chromosome 6</topic><topic>Chromosomes, Human, Pair 6 - genetics</topic><topic>European Continental Ancestry Group</topic><topic>Female</topic><topic>Genetics</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Heart</topic><topic>Humans</topic><topic>Lipoprotein(a) - genetics</topic><topic>Lipoproteins</topic><topic>Male</topic><topic>Mississippi</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk factors</topic><topic>Single-nucleotide polymorphism</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Jin</creatorcontrib><creatorcontrib>Lange, Leslie A</creatorcontrib><creatorcontrib>Sabourin, Jeremy</creatorcontrib><creatorcontrib>Duan, Qing</creatorcontrib><creatorcontrib>Valdar, William</creatorcontrib><creatorcontrib>Willis, Monte S</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Wilson, James G</creatorcontrib><creatorcontrib>Lange, Ethan M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</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>Engineering Research Database</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>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Jin</au><au>Lange, Leslie A</au><au>Sabourin, Jeremy</au><au>Duan, Qing</au><au>Valdar, William</au><au>Willis, Monte S</au><au>Li, Yun</au><au>Wilson, James G</au><au>Lange, Ethan M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study</atitle><jtitle>Journal of human genetics</jtitle><addtitle>J Hum Genet</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>60</volume><issue>12</issue><spage>755</spage><epage>761</epage><pages>755-761</pages><issn>1434-5161</issn><eissn>1435-232X</eissn><abstract>Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P<5 × 10(-8)) after adjusting for the local ancestry at 6q25.3. Interestingly, before adjusting for local ancestry, we observed significant (P<5 × 10(-8)) associations for hundreds of SNPs spanning ~10 Mb region on 6q surrounding the LPA gene, whereas after adjusting for local ancestry, the region containing significantly associated SNPs got much narrower and was centered over the LPA gene (<1 Mb). We observed a single nonsynonymous SNP in APOE significantly associated with Lp(a) (P<5 × 10(-8)). A high burden of coding variants in LPA and APOE were also associated with higher Lp(a) levels. Our study provides evidence that ancestry-specific causal risk variant(s) resides in or near LPA and that most of the observed associations outside this narrower region are spurious associations.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>26377243</pmid><doi>10.1038/jhg.2015.107</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | African Americans Age Apolipoprotein E Apolipoproteins Apolipoproteins E - genetics Body mass index Cardiovascular diseases Cardiovascular Diseases - genetics Chromosome 6 Chromosomes, Human, Pair 6 - genetics European Continental Ancestry Group Female Genetics Genome-Wide Association Study Genomes Genotype & phenotype Heart Humans Lipoprotein(a) - genetics Lipoproteins Male Mississippi Polymorphism, Single Nucleotide Risk factors Single-nucleotide polymorphism Studies |
| title | Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study |
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