Large-scale genome-wide association study of coronary artery disease in genetically diverse populations.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
25
02
2021
accepted:
08
06
2022
pubmed:
2
8
2022
medline:
23
8
2022
entrez:
1
8
2022
Statut:
ppublish
Résumé
We report a genome-wide association study (GWAS) of coronary artery disease (CAD) incorporating nearly a quarter of a million cases, in which existing studies are integrated with data from cohorts of white, Black and Hispanic individuals from the Million Veteran Program. We document near equivalent heritability of CAD across multiple ancestral groups, identify 95 novel loci, including nine on the X chromosome, detect eight loci of genome-wide significance in Black and Hispanic individuals, and demonstrate that two common haplotypes at the 9p21 locus are responsible for risk stratification in all populations except those of African origin, in which these haplotypes are virtually absent. Moreover, in the largest GWAS for angiographically derived coronary atherosclerosis performed to date, we find 15 loci of genome-wide significance that robustly overlap with established loci for clinical CAD. Phenome-wide association analyses of novel loci and polygenic risk scores (PRSs) augment signals related to insulin resistance, extend pleiotropic associations of these loci to include smoking and family history, and precisely document the markedly reduced transferability of existing PRSs to Black individuals. Downstream integrative analyses reinforce the critical roles of vascular endothelial, fibroblast, and smooth muscle cells in CAD susceptibility, but also point to a shared biology between atherosclerosis and oncogenesis. This study highlights the value of diverse populations in further characterizing the genetic architecture of CAD.
Identifiants
pubmed: 35915156
doi: 10.1038/s41591-022-01891-3
pii: 10.1038/s41591-022-01891-3
pmc: PMC9419655
mid: NIHMS1823613
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1679-1692Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG007419
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100046C
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85086
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100006C
Pays : United States
Organisme : BLRD VA
ID : I01 BX003340
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100002C
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008673
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008685
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100012C
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007417
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL103612
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008676
Pays : United States
Organisme : NIDDK NIH HHS
ID : UM1 DK126194
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK101478
Pays : United States
Organisme : BLRD VA
ID : I01 BX004821
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA229110
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011172
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100010C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100008C
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL080295
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004790
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM124836
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007416
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008657
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL130114
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200800007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL085251
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139865
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100011C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142302
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100003C
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007376
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL087652
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127564
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101478
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142017
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008672
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200036C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008679
Pays : United States
Organisme : CSRD VA
ID : IK2 CX001780
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114183
Pays : United States
Organisme : NIA NIH HHS
ID : HHSN271201100004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00006
Pays : United States
Organisme : BLRD VA
ID : I01 BX003362
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008680
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL150186
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85082
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100009C
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007843
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85083
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006379
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85079
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008664
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85080
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007397
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100001C
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008701
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC85081
Pays : United States
Informations de copyright
© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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