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Large-scale genome-wide association study of coronary artery disease in genetically diverse populations.
Wednesday,2022-10-12 15:59 America/Los_Angeles — ecterry
| Title | Large-scale genome-wide association study of coronary artery disease in genetically diverse populations. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Tcheandjieu, C, Zhu, X, Hilliard, AT, Clarke, SL, Napolioni, V, Ma, S, Lee, KMin, Fang, H, Chen, F, Lu, Y, Tsao, NL, Raghavan, S, Koyama, S, Gorman, BR, Vujkovic, M, Klarin, D, Levin, MG, Sinnott-Armstrong, N, Wojcik, GL, Plomondon, ME, Maddox, TM, Waldo, SW, Bick, AG, Pyarajan, S, Huang, J, Song, R, Ho, Y-L, Buyske, S, Kooperberg, C, Haessler, J, Loos, RJF, Do, R, Verbanck, M, Chaudhary, K, North, KE, Avery, CL, Graff, M, Haiman, CA, Le Marchand, L, Wilkens, LR, Bis, JC, Leonard, H, Shen, B, Lange, LA, Giri, A, Dikilitas, O, Kullo, IJ, Stanaway, IB, Jarvik, GP, Gordon, AS, Hebbring, S, Namjou, B, Kaufman, KM, Ito, K, Ishigaki, K, Kamatani, Y, Verma, SS, Ritchie, MD, Kember, RL, Baras, A, Lotta, LA, Kathiresan, S, Hauser, ER, Miller, DR, Lee, JS, Saleheen, D, Reaven, PD, Cho, K, J Gaziano, M, Natarajan, P, Huffman, JE, Voight, BF, Rader, DJ, Chang, K-M, Lynch, JA, Damrauer, SM, Wilson, PWF, Tang, H, Sun, YV, Tsao, PS, O'Donnell, CJ, Assimes, TL |
| Corporate/Institutional Authors | Regeneron Genetics Center, CARDIoGRAMplusC4D Consortium, Biobank Japan, Million Veteran Program |
| Journal | Nat Med |
| Volume | 28 |
| Issue | 8 |
| Pagination | 1679-1692 |
| Date Published | 2022 08 |
| ISSN | 1546-170X |
| Keywords | Coronary Artery Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41591-022-01891-3 |
| Alternate Journal | Nat Med |
| PubMed ID | 35915156 |
| PubMed Central ID | PMC9419655 |
| Grant List | N01HC85086 / HL / NHLBI NIH HHS / United States I01 BX003340 / BX / BLRD VA / United States HHSN268201100002C / WH / WHI NIH HHS / United States U01 HG008685 / HG / NHGRI NIH HHS / United States HHSN268201100004C / WH / WHI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States U01 HG007417 / HG / NHGRI NIH HHS / United States U01 HG006385 / HG / NHGRI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States U01 HG008676 / HG / NHGRI NIH HHS / United States U01 HG006375 / HG / NHGRI NIH HHS / United States U01 HG007419 / HG / NHGRI NIH HHS / United States U01 HG004438 / HG / NHGRI NIH HHS / United States R56 DK101478 / DK / NIDDK NIH HHS / United States I01 BX004821 / BX / BLRD VA / United States R01 HL120393 / HL / NHLBI NIH HHS / United States T32 CA229110 / CA / NCI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States R35 GM124836 / GM / NIGMS NIH HHS / United States U01 HG007416 / HG / NHGRI NIH HHS / United States U01 HG008657 / HG / NHGRI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States U01 HG006382 / HG / NHGRI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States S10 OD028685 / OD / NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States R01 HL139865 / HL / NHLBI NIH HHS / United States HHSN268201100046C / HL / NHLBI NIH HHS / United States U01 HG011719 / HG / NHGRI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States U01 HG004603 / HG / NHGRI NIH HHS / United States R01 HL142302 / HL / NHLBI NIH HHS / United States HHSN268201100003C / WH / WHI NIH HHS / United States U01 HG007376 / HG / NHGRI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 HL127564 / HL / NHLBI NIH HHS / United States U01 HG004424 / HG / NHGRI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U01 HG006389 / HG / NHGRI NIH HHS / United States R01 DK101478 / DK / NIDDK NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 HG004609 / HG / NHGRI NIH HHS / United States R01 HL142017 / HL / NHLBI NIH HHS / United States U01 HG008672 / HG / NHGRI NIH HHS / United States R01 HL142711 / HL / NHLBI NIH HHS / United States U01 HG004599 / HG / NHGRI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States U01 HG008684 / HG / NHGRI NIH HHS / United States K23 AG000989 / AG / NIA NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States U01 HG006828 / HG / NHGRI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States U01 HG008679 / HG / NHGRI NIH HHS / United States IK2 CX001780 / CX / CSRD VA / United States R01 DK114183 / DK / NIDDK NIH HHS / United States R01 HL151152 / HL / NHLBI NIH HHS / United States HHSN271201100004C / AG / NIA NIH HHS / United States U01 HG006380 / HG / NHGRI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States U01 HG006388 / HG / NHGRI NIH HHS / United States I01 BX003362 / BX / BLRD VA / United States U01 HG008680 / HG / NHGRI NIH HHS / United States R56 HL150186 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States U01 HG006378 / HG / NHGRI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States U01 HG004610 / HG / NHGRI NIH HHS / United States U01 HG008673 / HG / NHGRI NIH HHS / United States U01 HG006379 / HG / NHGRI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States U01 HG008664 / HG / NHGRI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States U01 HG007397 / HG / NHGRI NIH HHS / United States U01 HG004608 / HG / NHGRI NIH HHS / United States HHSN268201100001C / WH / WHI NIH HHS / United States U01 CA164973 / CA / NCI NIH HHS / United States R01 HL148050 / HL / NHLBI NIH HHS / United States U01 HG008701 / HG / NHGRI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States U01 HG006830 / HG / NHGRI NIH HHS / United States |
ePub date:
22/08