Variation in LPA is associated with Lp(a) levels in three populations from the Third National Health and Nutrition Examination Survey
The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third...
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description | The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p |
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The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18 × 10(-30)). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0016604</identifier><identifier>PMID: 21305047</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>African Americans ; Apolipoproteins ; Biology ; Biophysics ; Black People - genetics ; Cardiovascular disease ; Deoxyribonucleic acid ; Disease control ; DNA ; Genetic diversity ; Genetic research ; Genetic Variation ; Genetics ; Genomes ; Genomics ; Genotype ; Genotype & phenotype ; Health surveys ; Hispanic Americans ; Hispanic or Latino - genetics ; Humans ; Lipoprotein A ; Lipoprotein(a) - blood ; Lipoprotein(a) - genetics ; Lipoproteins ; Medicine ; Minority & ethnic groups ; Nutrition ; Physiology ; Polymorphism ; Polymorphism, Single Nucleotide ; Population ; Population Groups - genetics ; Populations ; Procedure manuals ; Single-nucleotide polymorphism ; Social and Behavioral Sciences ; Studies ; Subpopulations ; Surveys ; White People - genetics</subject><ispartof>PloS one, 2011-01, Vol.6 (1), p.e16604</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Dumitrescu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Dumitrescu et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-c93ed410ee5386f030df01e51fbc2d1d3b7dd2d90f959b01da6232eb4af77d613</citedby><cites>FETCH-LOGICAL-c592t-c93ed410ee5386f030df01e51fbc2d1d3b7dd2d90f959b01da6232eb4af77d613</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/PMC3030597/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030597/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21305047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kloss-Brandstaetter, Anita</contributor><creatorcontrib>Dumitrescu, Logan</creatorcontrib><creatorcontrib>Glenn, Kimberly</creatorcontrib><creatorcontrib>Brown-Gentry, Kristin</creatorcontrib><creatorcontrib>Shephard, Cynthia</creatorcontrib><creatorcontrib>Wong, Michelle</creatorcontrib><creatorcontrib>Rieder, Mark J</creatorcontrib><creatorcontrib>Smith, Joshua D</creatorcontrib><creatorcontrib>Nickerson, Deborah A</creatorcontrib><creatorcontrib>Crawford, Dana C</creatorcontrib><title>Variation in LPA is associated with Lp(a) levels in three populations from the Third National Health and Nutrition Examination Survey</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. 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blood</subject><subject>Lipoprotein(a) - genetics</subject><subject>Lipoproteins</subject><subject>Medicine</subject><subject>Minority & ethnic groups</subject><subject>Nutrition</subject><subject>Physiology</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Population Groups - genetics</subject><subject>Populations</subject><subject>Procedure manuals</subject><subject>Single-nucleotide polymorphism</subject><subject>Social and Behavioral Sciences</subject><subject>Studies</subject><subject>Subpopulations</subject><subject>Surveys</subject><subject>White People - genetics</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</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>eNptUs1uEzEYXCEQLYU3QGCJA3BI8M-uN74gRVWhlSJAonC1vPbnxJGzXuzdQB-A98ZJtlWDKh9sjWfm-9EUxUuCp4TV5MM6DLFVftqFFqYYE85x-ag4JYLRCaeYPb73PimepbTGuGIzzp8WJ5QwXOGyPi3-_lTRqd6FFrkWLb7NkUtIpRR0RsGg365foUX3Tr1HHrbg047WryIA6kI3-L00IRvDJsOArlcuGvRlDyuPLkH5bKDajA19dPtCF3_UxrWHot-HuIWb58UTq3yCF-N9Vvz4dHF9fjlZfP18dT5fTHQlaD_RgoEpCQbYDWIxw8ZiAhWxjaaGGNbUxlAjsBWVaDAxilNGoSmVrWvDCTsrXh98Ox-SHDeYJKGiJIKXFc2MqwPDBLWWXXQbFW9kUE7ugRCXUsXeaQ8Sz5ipmFWClmXJG650o9mMKGqJANZU2evjWG1oNmA0tH1U_sj0-Kd1K7kMW8nyZJWos8Hb0SCGXwOkXm5c0uC9aiEMSc4qQikXGGfmm_-YDw83spYq9-9aG3JZvfOU87LORpzPeGZNH2DlY2DjdE6bdRk_EpQHgY4hpQj2bkSC5S6rt83IXVblmNUse3V_PXei23Cyf6h857M</recordid><startdate>20110128</startdate><enddate>20110128</enddate><creator>Dumitrescu, Logan</creator><creator>Glenn, Kimberly</creator><creator>Brown-Gentry, Kristin</creator><creator>Shephard, Cynthia</creator><creator>Wong, Michelle</creator><creator>Rieder, Mark J</creator><creator>Smith, Joshua D</creator><creator>Nickerson, Deborah A</creator><creator>Crawford, Dana C</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>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>AEUYN</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>20110128</creationdate><title>Variation in LPA is associated with Lp(a) levels in three populations from the Third National Health and Nutrition Examination Survey</title><author>Dumitrescu, Logan ; Glenn, Kimberly ; Brown-Gentry, Kristin ; Shephard, Cynthia ; Wong, Michelle ; Rieder, Mark J ; Smith, Joshua D ; Nickerson, Deborah A ; Crawford, Dana C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c592t-c93ed410ee5386f030df01e51fbc2d1d3b7dd2d90f959b01da6232eb4af77d613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>African Americans</topic><topic>Apolipoproteins</topic><topic>Biology</topic><topic>Biophysics</topic><topic>Black People - 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The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18 × 10(-30)). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21305047</pmid><doi>10.1371/journal.pone.0016604</doi><oa>free_for_read</oa></addata></record> |
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subjects | African Americans Apolipoproteins Biology Biophysics Black People - genetics Cardiovascular disease Deoxyribonucleic acid Disease control DNA Genetic diversity Genetic research Genetic Variation Genetics Genomes Genomics Genotype Genotype & phenotype Health surveys Hispanic Americans Hispanic or Latino - genetics Humans Lipoprotein A Lipoprotein(a) - blood Lipoprotein(a) - genetics Lipoproteins Medicine Minority & ethnic groups Nutrition Physiology Polymorphism Polymorphism, Single Nucleotide Population Population Groups - genetics Populations Procedure manuals Single-nucleotide polymorphism Social and Behavioral Sciences Studies Subpopulations Surveys White People - genetics |
title | Variation in LPA is associated with Lp(a) levels in three populations from the Third National Health and Nutrition Examination Survey |
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