Title | Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Bis, JC, Kavousi, M, Franceschini, N, Isaacs, A, Abecasis, GR, Schminke, U, Post, WS, Smith, AV, Cupples, AL, Markus, HS, Schmidt, R, Huffman, JE, Lehtimäki, T, Baumert, J, Münzel, T, Heckbert, SR, Dehghan, A, North, K, Oostra, B, Bevan, S, Stoegerer, E-M, Hayward, C, Raitakari, O, Meisinger, C, Schillert, A, Sanna, S, Völzke, H, Cheng, Y-C, Thorsson, B, Fox, CS, Rice, K, Rivadeneira, F, Nambi, V, Halperin, E, Petrovic, KE, Peltonen, L, Wichmann, EH, Schnabel, RB, Dörr, M, Parsa, A, Aspelund, T, Demissie, S, Kathiresan, S, Reilly, MP, Taylor, K, Uitterlinden, A, Couper, DJ, Sitzer, M, Kähönen, M, Illig, T, Wild, PS, Orrù, M, Lüdemann, J, Shuldiner, AR, Eiriksdottir, G, White, CC, Rotter, JI, Hofman, A, Seissler, J, Zeller, T, Usala, G, Ernst, F, Launer, LJ, D'Agostino, RB, O'Leary, DH, Ballantyne, C, Thiery, J, Ziegler, A, Lakatta, EG, Chilukoti, RKumar, Harris, TB, Wolf, PA, Psaty, BM, Polak, JF, Li, X, Rathmann, W, Uda, M, Boerwinkle, E, Klopp, N, Schmidt, H, Wilson, JF, Viikari, J, Koenig, W, Blankenberg, S, Newman, AB, Witteman, J, Heiss, G, van Duijn, C, Scuteri, A, Homuth, G, Mitchell, BD, Gudnason, V, O'Donnell, CJ |
Corporate/Institutional Authors | CARDIoGRAM consortium |
Journal | Nat Genet |
Volume | 43 |
Issue | 10 |
Pagination | 940-7 |
Date Published | 2011 Sep 11 |
ISSN | 1546-1718 |
Keywords | Adult, Aged, Aging, Atherosclerosis, Carotid Intima-Media Thickness, Cohort Studies, Coronary Artery Disease, European Continental Ancestry Group, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Heart, Humans, Middle Aged, Phenotype, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide, Risk Factors |
Abstract | <p>Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.</p> |
DOI | 10.1038/ng.920 |
Alternate Journal | Nat. Genet. |
PubMed ID | 21909108 |
PubMed Central ID | PMC3257519 |
Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States CZB/4/710 / / Chief Scientist Office / United Kingdom UL1 TR000005 / TR / NCATS NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States R01 AG016495 / AG / NIA NIH HHS / United States U01 HL084729 / HL / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-AG-1-2109 / AG / NIA NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States MC_U127561128 / / Medical Research Council / United Kingdom N01 HC015103 / HC / NHLBI NIH HHS / United States M01 RR000069 / RR / NCRR NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 AG18728 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States U01 GM074518-04 / GM / NIGMS NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States M01 RR 16500 / RR / NCRR NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States AG08122 / AG / NIA NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States HL084729 / HL / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States 268200625226C / / PHS HHS / United States HL075366 / HL / NHLBI NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States P30 DK072488 / DK / NIDDK NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States M01RR00069 / RR / NCRR NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States U01 HL072515 / HL / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States M01 RR016500 / RR / NCRR NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States Z99 HL999999 / / Intramural NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States AG16495 / AG / NIA NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States / / Chief Scientist Office / United Kingdom HL080295 / HL / NHLBI NIH HHS / United States HG005581 / HG / NHGRI NIH HHS / United States U01 HL072515-06 / HL / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States RC2 HG005581 / HG / NHGRI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 AG018728 / AG / NIA NIH HHS / United States U01 GM074518 / GM / NIGMS NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States Z01 HL006002-01 / / Intramural NIH HHS / United States R01 HL088119 / HL / NHLBI NIH HHS / United States |