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Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

TitleFine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.
Publication TypeJournal Article
Year of Publication2016
AuthorsZubair N, Graff M, Ambite JLuis, Bush WS, Kichaev G, Lu Y, Manichaikul A, Sheu WH-H, Absher D, Assimes TL, Bielinski SJ, Bottinger EP, Bůžková P, Chuang L-M, Chung R-H, Cochran B, Dumitrescu L, Gottesman O, Haessler JW, Haiman C, Heiss G, Hsiung CA, Hung Y-J, Hwu C-M, Juang J-MJ, Le Marchand L, Lee I-T, Lee W-J, Lin L-A, Lin D, Lin S-Y, Mackey RH, Martin LW, Pasaniuc B, Peters U, Predazzi I, Quertermous T, Reiner AP, Robinson J, Rotter JI, Ryckman KK, Schreiner PJ, Stahl E, Tao R, Tsai MY, Waite LL, Wang T-D, Buyske S, Chen Y-DIda, Cheng I, Crawford DC, Loos RJF, Rich SS, Fornage M, North KE, Kooperberg C
Secondary AuthorsCarty CL
JournalHum Mol Genet
Volume25
Issue24
Pagination5500-5512
Date Published2016 12 15
ISSN1460-2083
KeywordsAfrican Americans, Apolipoprotein A-V, Asian Continental Ancestry Group, ATP Binding Cassette Transporter, Subfamily G, Member 8, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Hispanic Americans, Humans, Indians, North American, Lipids, Lipoprotein Lipase, Male, Triglycerides
Abstract

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies.

DOI10.1093/hmg/ddw358
Alternate JournalHum Mol Genet
PubMed ID28426890
PubMed Central IDPMC5721937
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
U01 HG007376 / HG / NHGRI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
U01 HG007419 / HG / NHGRI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States