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Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study.
Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
| Title | Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Franceschini, N, Carty, C, Bůzková, P, Reiner, AP, Garrett, T, Lin, Y, Vöckler, J-S, Hindorff, LA, Cole, SA, Boerwinkle, E, Lin, D-Y, Bookman, E, Best, LG, Bella, JN, Eaton, C, Greenland, P, Jenny, N, North, KE, Taverna, D, Young, AM, Deelman, E, Kooperberg, C, Psaty, B, Heiss, G |
| Journal | Circ Cardiovasc Genet |
| Volume | 4 |
| Issue | 6 |
| Pagination | 661-72 |
| Date Published | 2011 Dec |
| ISSN | 1942-3268 |
| Keywords | Aged, Aged, 80 and over, Continental Population Groups, Coronary Disease, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies |
| Abstract | <p><b>BACKGROUND: </b>Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts.</p><p><b>METHODS AND RESULTS: </b>The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hispanic individuals (113 events), 3669 American Indian individuals (595 events), and 885 Asian/Pacific Islander individuals (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex, and ancestry (as needed). Nine loci were statistically associated with incident CHD events in white participants: 9p21 (rs10757278; P=4.7 × 10(-41)), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7 × 10(-6)), MTHFD1L (rs6922269, P=5.1 × 10(-10)), APOE (rs429358; P=2.7×10(-18)), ZNF627 (rs4804611; P=5.0 × 10(-8)), CXCL12 (rs501120; P=1.4 × 10(-6)) and LPL (rs268; P=2.7 × 10(-17)). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals age 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in black participants, and associations varied in other US minorities.</p><p><b>CONCLUSIONS: </b>Prospective analyses of white participants replicated several reported cross-sectional CHD-SNP associations.</p> |
| DOI | 10.1161/CIRCGENETICS.111.960096 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 22042884 |
| PubMed Central ID | PMC3293207 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States M01-RR00425 / RR / NCRR NIH HHS / United States N01-HC-45205 / HC / NHLBI NIH HHS / United States U01 HL041642 / HL / NHLBI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States U01 HL65520 / HL / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States U01 HL041654 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States U01 HL65521 / HL / NHLBI NIH HHS / United States N01HC48049 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States U01 HG004802 / HG / NHGRI NIH HHS / United States N01HC45205 / HL / NHLBI NIH HHS / United States U01 HL41642 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States 32118 / / PHS HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States 32115 / / PHS HHS / United States 32109 / / PHS HHS / United States U01HG004803 / HG / NHGRI NIH HHS / United States UL1 RR025741 / RR / NCRR NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01-HC-95095 / HC / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States 42126 / / PHS HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States U01 HL041652 / HL / NHLBI NIH HHS / United States U01HG004802 / HG / NHGRI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 24152 / / PHS HHS / United States 32119 / / PHS HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States U01 HL41654 / HL / NHLBI NIH HHS / United States 32108 / / PHS HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States 42132 / / PHS HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States N01HC95095 / HL / NHLBI NIH HHS / United States U01 HL41652 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States U01 HG004803 / HG / NHGRI NIH HHS / United States N01-HC-48049 / HC / NHLBI NIH HHS / United States U01HG004798 / HG / NHGRI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01 HC045134 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States 32106 / / PHS HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States N01HC48050 / HL / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC05187 / HL / NHLBI NIH HHS / United States U01HG004801 / HG / NHGRI NIH HHS / United States N01HC48047 / HL / NHLBI NIH HHS / United States U01 HL065521 / HL / NHLBI NIH HHS / United States 32102 / / PHS HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States U01HG004790 / HG / NHGRI NIH HHS / United States U01 HG004798 / HG / NHGRI NIH HHS / United States 32105 / / PHS HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States 42129 / / PHS HHS / United States 32113 / / PHS HHS / United States 32122 / / PHS HHS / United States U01HG004801-01 / HG / NHGRI NIH HHS / United States 42107 / / PHS HHS / United States 32100 / / PHS HHS / United States N01-HC-48048 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States 32111 / / PHS HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States 44221 / / PHS HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States U01 HL065520 / HL / NHLBI NIH HHS / United States U01 HG004803-04 / HG / NHGRI NIH HHS / United States N01HC48048 / HL / NHLBI NIH HHS / United States U01 HG004801 / HG / NHGRI NIH HHS / United States |