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Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

TitleTrans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.
Publication TypeJournal Article
Year of Publication2013
AuthorsWu Y, Waite LL, Jackson AU, Sheu WH-H, Buyske S, Absher D, Arnett DK, Boerwinkle E, Bonnycastle LL, Carty CL, Cheng I, Cochran B, Croteau-Chonka DC, Dumitrescu L, Eaton CB, Franceschini N, Guo X, Henderson BE, Hindorff LA, Kim E, Kinnunen L, Komulainen P, Lee W-J, Le Marchand L, Lin Y, Lindström J, Lingaas-Holmen O, Mitchell SL, Narisu N, Robinson JG, Schumacher F, Stancáková A, Sundvall J, Sung Y-J, Swift AJ, Wang W-C, Wilkens L, Wilsgaard T, Young AM, Adair LS, Ballantyne CM, Bůžková P, Chakravarti A, Collins FS, Duggan D, Feranil AB, Ho L-T, Hung Y-J, Hunt SC, Hveem K, Juang J-MJ, Kesäniemi AY, Kuusisto J, Laakso M, Lakka TA, Lee I-T, Leppert MF, Matise TC, Moilanen L, Njølstad I, Peters U, Quertermous T, Rauramaa R, Rotter JI, Saramies J, Tuomilehto J, Uusitupa M, Wang T-D, Boehnke M, Haiman CA, Chen Y-DI, Kooperberg C, Assimes TL, Crawford DC, Hsiung CA, North KE
Secondary AuthorsMohlke KL
JournalPLoS Genet
Volume9
Issue3
Paginatione1003379
Date Published2013 Mar
ISSN1553-7404
KeywordsAfrican Americans, Apolipoprotein A-V, Apolipoproteins A, Cholesterol, HDL, Cholesterol, LDL, European Continental Ancestry Group, Genome-Wide Association Study, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Proprotein Convertase 9, Proprotein Convertases, Serine Endopeptidases, Triglycerides
Abstract

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P

DOI10.1371/journal.pgen.1003379
Alternate JournalPLoS Genet
PubMed ID23555291
PubMed Central IDPMC3605054
Grant ListR01 DK093757 / DK / NIDDK NIH HHS / United States
DK078150 / DK / NIDDK NIH HHS / United States
32105-6 / / PHS HHS / United States
DK093757 / DK / NIDDK NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
U01CA98758 / CA / NCI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
2 R01 HL55673-12 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
42107-26 / / PHS HHS / United States
32115 / / PHS HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
1Z01-HG000024 / HG / NHGRI NIH HHS / United States
R01 HG000376 / HG / NHGRI NIH HHS / United States
U01CA136792 / CA / NCI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
HL54515 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
HL54497 / HL / NHLBI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
ES10126 / ES / NIEHS NIH HHS / United States
32100-2 / / PHS HHS / United States
R56 HG000376 / HG / NHGRI NIH HHS / United States
24152 / / PHS HHS / United States
TW05596 / TW / FIC NIH HHS / United States
DK072193 / DK / NIDDK NIH HHS / United States
DK56350 / DK / NIDDK NIH HHS / United States
RR20649 / RR / NCRR NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
42129-32 / / PHS HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
HL085144 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
HL54496 / HL / NHLBI NIH HHS / United States
32118-32119 / / PHS HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
32108-9 / / PHS HHS / United States
HL54473 / HL / NHLBI NIH HHS / United States
T32 GM007092 / GM / NIGMS NIH HHS / United States
DK062370 / DK / NIDDK NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
R37CA54281 / CA / NCI NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
32122 / / PHS HHS / United States
U01HG004801-01 / HG / NHGRI NIH HHS / United States
HL54495 / HL / NHLBI NIH HHS / United States
HL087647 / HL / NHLBI NIH HHS / United States
R24 HD050924 / HD / NICHD NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
44221 / / PHS HHS / United States
32111-13 / / PHS HHS / United States
HL54471 / HL / NHLBI NIH HHS / United States
HL54509 / HL / NHLBI NIH HHS / United States
P01CA33619 / CA / NCI NIH HHS / United States
HL54472 / HL / NHLBI NIH HHS / United States
R01 CA63 / CA / NCI NIH HHS / United States