Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispani...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0050198&type=printable |
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| author | Clara C Elbers Yiran Guo Vinicius Tragante Erik P A van Iperen Matthew B Lanktree Berta Almoguera Castillo Fang Chen Lisa R Yanek Mary K Wojczynski Yun R Li Bart Ferwerda Christie M Ballantyne Sarah G Buxbaum Yii-Der Ida Chen Wei-Min Chen L Adrienne Cupples Mary Cushman Yanan Duan David Duggan Michele K Evans Jyotika K Fernandes Myriam Fornage Melissa Garcia W Timothy Garvey Nicole Glazer Felicia Gomez Tamara B Harris Indrani Halder Virginia J Howard Margaux F Keller M Ilyas Kamboh Charles Kooperberg Stephen B Kritchevsky Andrea LaCroix Kiang Liu Yongmei Liu Kiran Musunuru Anne B Newman N Charlotte Onland-Moret Jose Ordovas Inga Peter Wendy Post Susan Redline Steven E Reis Richa Saxena Pamela J Schreiner Kelly A Volcik Xingbin Wang Salim Yusuf Alan B Zonderland Sonia S Anand Diane M Becker Bruce Psaty Daniel J Rader Alex P Reiner Stephen S Rich Jerome I Rotter Michèle M Sale Michael Y Tsai Ingrid B Borecki Robert A Hegele Sekar Kathiresan Michael A Nalls Herman A Taylor Hakon Hakonarson Suthesh Sivapalaratnam Folkert W Asselbergs Fotios Drenos James G Wilson Brendan J Keating |
| author_facet | Clara C Elbers Yiran Guo Vinicius Tragante Erik P A van Iperen Matthew B Lanktree Berta Almoguera Castillo Fang Chen Lisa R Yanek Mary K Wojczynski Yun R Li Bart Ferwerda Christie M Ballantyne Sarah G Buxbaum Yii-Der Ida Chen Wei-Min Chen L Adrienne Cupples Mary Cushman Yanan Duan David Duggan Michele K Evans Jyotika K Fernandes Myriam Fornage Melissa Garcia W Timothy Garvey Nicole Glazer Felicia Gomez Tamara B Harris Indrani Halder Virginia J Howard Margaux F Keller M Ilyas Kamboh Charles Kooperberg Stephen B Kritchevsky Andrea LaCroix Kiang Liu Yongmei Liu Kiran Musunuru Anne B Newman N Charlotte Onland-Moret Jose Ordovas Inga Peter Wendy Post Susan Redline Steven E Reis Richa Saxena Pamela J Schreiner Kelly A Volcik Xingbin Wang Salim Yusuf Alan B Zonderland Sonia S Anand Diane M Becker Bruce Psaty Daniel J Rader Alex P Reiner Stephen S Rich Jerome I Rotter Michèle M Sale Michael Y Tsai Ingrid B Borecki Robert A Hegele Sekar Kathiresan Michael A Nalls Herman A Taylor Hakon Hakonarson Suthesh Sivapalaratnam Folkert W Asselbergs Fotios Drenos James G Wilson Brendan J Keating |
| author_sort | Clara C Elbers |
| collection | DOAJ |
| description | Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report. |
| format | Article |
| id | doaj-art-61a34aa47fe44caabf48c32acc494970 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-61a34aa47fe44caabf48c32acc4949702025-08-20T03:10:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5019810.1371/journal.pone.0050198Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.Clara C ElbersYiran GuoVinicius TraganteErik P A van IperenMatthew B LanktreeBerta Almoguera CastilloFang ChenLisa R YanekMary K WojczynskiYun R LiBart FerwerdaChristie M BallantyneSarah G BuxbaumYii-Der Ida ChenWei-Min ChenL Adrienne CupplesMary CushmanYanan DuanDavid DugganMichele K EvansJyotika K FernandesMyriam FornageMelissa GarciaW Timothy GarveyNicole GlazerFelicia GomezTamara B HarrisIndrani HalderVirginia J HowardMargaux F KellerM Ilyas KambohCharles KooperbergStephen B KritchevskyAndrea LaCroixKiang LiuYongmei LiuKiran MusunuruAnne B NewmanN Charlotte Onland-MoretJose OrdovasInga PeterWendy PostSusan RedlineSteven E ReisRicha SaxenaPamela J SchreinerKelly A VolcikXingbin WangSalim YusufAlan B ZonderlandSonia S AnandDiane M BeckerBruce PsatyDaniel J RaderAlex P ReinerStephen S RichJerome I RotterMichèle M SaleMichael Y TsaiIngrid B BoreckiRobert A HegeleSekar KathiresanMichael A NallsHerman A TaylorHakon HakonarsonSuthesh SivapalaratnamFolkert W AsselbergsFotios DrenosJames G WilsonBrendan J KeatingMeta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0050198&type=printable |
| spellingShingle | Clara C Elbers Yiran Guo Vinicius Tragante Erik P A van Iperen Matthew B Lanktree Berta Almoguera Castillo Fang Chen Lisa R Yanek Mary K Wojczynski Yun R Li Bart Ferwerda Christie M Ballantyne Sarah G Buxbaum Yii-Der Ida Chen Wei-Min Chen L Adrienne Cupples Mary Cushman Yanan Duan David Duggan Michele K Evans Jyotika K Fernandes Myriam Fornage Melissa Garcia W Timothy Garvey Nicole Glazer Felicia Gomez Tamara B Harris Indrani Halder Virginia J Howard Margaux F Keller M Ilyas Kamboh Charles Kooperberg Stephen B Kritchevsky Andrea LaCroix Kiang Liu Yongmei Liu Kiran Musunuru Anne B Newman N Charlotte Onland-Moret Jose Ordovas Inga Peter Wendy Post Susan Redline Steven E Reis Richa Saxena Pamela J Schreiner Kelly A Volcik Xingbin Wang Salim Yusuf Alan B Zonderland Sonia S Anand Diane M Becker Bruce Psaty Daniel J Rader Alex P Reiner Stephen S Rich Jerome I Rotter Michèle M Sale Michael Y Tsai Ingrid B Borecki Robert A Hegele Sekar Kathiresan Michael A Nalls Herman A Taylor Hakon Hakonarson Suthesh Sivapalaratnam Folkert W Asselbergs Fotios Drenos James G Wilson Brendan J Keating Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. PLoS ONE |
| title | Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. |
| title_full | Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. |
| title_fullStr | Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. |
| title_full_unstemmed | Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. |
| title_short | Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations. |
| title_sort | gene centric meta analysis of lipid traits in african east asian and hispanic populations |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0050198&type=printable |
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