Journal
NATURE
Volume 466, Issue 7307, Pages 707-713Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature09270
Keywords
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Categories
Funding
- British Heart Foundation [PG/08/094/26019, SP/08/005/25115, PG/08/094, RG/07/005/23633, PG/02/128] Funding Source: Medline
- FIC NIH HHS [TW05596] Funding Source: Medline
- Intramural NIH HHS Funding Source: Medline
- Medical Research Council [G0601966, G0701863, MC_QA137934, G0000934, MC_U106188470, G0401527, G0801056, G0801566, G9521010D, G9521010, MC_U106179471, MC_U127561128, G0700931] Funding Source: Medline
- NCI NIH HHS [CA 047988] Funding Source: Medline
- NCRR NIH HHS [M01-RR00425, RR20649, U54 RR020278, UL1RR025005] Funding Source: Medline
- NHGRI NIH HHS [N01-HG-65403, 1Z01 HG000024, T32 HG000040, U01HG004402, T32 HG00040] Funding Source: Medline
- NHLBI NIH HHS [RC2 HL101864,, RC1 HL099634, N01-HC-55021, N01-HC-85086, HL-54776, N01-HC-85082, N01-HC-35129, N01 HC-55222, N01-HC-55019, HL085144, R01HL087641, N01-HC-55015, N01-HC-85083, N01-HC-75150, N01-HC-55020, N01-HC-85080, N01 HC-15103, U01 HL069757, 5R01HL08821502, R01 HL089650, R01HL086694, N01-HC-85084, K99 HL098364, HL 04381, N01-HC-55018, R01HL087652, 5R01HL08770003, T32HL007208, N01-HC-45133, K99 HL098364-01, N01-HC-85079, U01 HL080295, 5R01HL087679-02, RC1 HL099634-02, N02-HL-6-4278, N01-HC-25195, R01 HL087676, K99HL094535, N01-HC-85085, R01HL59367, R01 HL089309, RC1 HL099793, RC2 HL102419, N01-HC-55022, N01-HC-85081, N01-HC-55016, HL 080467] Funding Source: Medline
- NIA NIH HHS [N01-AG-12100] Funding Source: Medline
- NICHD NIH HHS [R24 HD050924] Funding Source: Medline
- NIDDK NIH HHS [U01 DK062370, U01 DK062418, 5R01DK07568102, 5R01DK06833603, DK062370, R01 DK072193, DK078150, DK063491, R01 DK078150, DK072193, DK56350] Funding Source: Medline
- NIEHS NIH HHS [ES10126] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007092] Funding Source: Medline
- PHS HHS [HHSN268200625226C] Funding Source: Medline
- Wellcome Trust [077016/Z/05/Z, 079895, 068545/Z/02, 076113/B/04/Z] Funding Source: Medline
- Chief Scientist Office [CZB/4/710] Funding Source: Medline
- British Heart Foundation [PG/08/094/26019] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Medical Research Council [G9521010, MC_U127561128, MC_qA137934, G0801056, G0700931, G0401527, G0000934, G0801056B, G0601966, G0701863, G0801566, MC_U106179471, MC_U106188470] Funding Source: researchfish
- MRC [G9521010, G0801566, G0701863, G0000934, G0700931, G0801056, MC_U127561128, G0601966, MC_U106188470, MC_qA137934] Funding Source: UKRI
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Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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