BACKGROUND: Genome-wide association studies have identified loci associated with coronary heart disease in whites of European ancestry. This study evaluated whether genetic markers previously identified in whites are associated with nonfatal acute myocardial infarction (MI) in Hispanics. METHODS AND RESULTS: Cases (n=1989) with a first nonfatal acute MI and population-based controls (n=2096) living in Costa Rica were studied. Fourteen single-nucleotide polymorphisms were genotyped. Seven single-nucleotide polymorphisms at 3 independent loci showed significant associations with MI. The odds ratios for the loci with the strongest associations were 1.16 (95 confidence interval [CI], 1.05 to 1.27) for rs4977574 (CDKN2A/2B), 1.15 (95 CI, 1.03 to 1.29) for rs646776 (CELSR2-PSRC1-SORT1), and 1.22 (95 CI, 1.08 to 1.38) for rs501120 (CXCL12); the corresponding PARs were 6.8, 10.5, and 15.2; respectively. We developed a genetic risk score by summing the number of the top 3 associated risk alleles. The OR for MI per genetic risk score unit was 1.18 (95 CI, 1.11 to 1.25; P=4.83 × 10(-8)). Discrimination of MI was significantly improved (P=0.02) when the genetic risk score was added to a model including clinical predictors. However, the increase in the area under the receiver-operating characteristic curve after the genetic risk score was added was moderate, from 0.67 (95 CI, 0.65 to 0.69) to 0.68 (95 CI, 0.66 to 0.70). CONCLUSIONS: These results indicate both the consistency and disparity of genetic effects on risk of MI between Hispanic and white populations. The improvement in the identified genetic markers on discrimination of MI in Hispanics was modest.
BACKGROUND: Genome-wide association studies have identified loci associated with coronary heart disease in whites of European ancestry. This study evaluated whether genetic markers previously identified in whites are associated with nonfatal acute myocardial infarction (MI) in Hispanics. METHODS AND RESULTS: Cases (n=1989) with a first nonfatal acute MI and population-based controls (n=2096) living in Costa Rica were studied. Fourteen single-nucleotide polymorphisms were genotyped. Seven single-nucleotide polymorphisms at 3 independent loci showed significant associations with MI. The odds ratios for the loci with the strongest associations were 1.16 (95 confidence interval [CI], 1.05 to 1.27) for rs4977574 (CDKN2A/2B), 1.15 (95 CI, 1.03 to 1.29) for rs646776 (CELSR2-PSRC1-SORT1), and 1.22 (95 CI, 1.08 to 1.38) for rs501120 (CXCL12); the corresponding PARs were 6.8, 10.5, and 15.2; respectively. We developed a genetic risk score by summing the number of the top 3 associated risk alleles. The OR for MI per genetic risk score unit was 1.18 (95 CI, 1.11 to 1.25; P=4.83 × 10(-8)). Discrimination of MI was significantly improved (P=0.02) when the genetic risk score was added to a model including clinical predictors. However, the increase in the area under the receiver-operating characteristic curve after the genetic risk score was added was moderate, from 0.67 (95 CI, 0.65 to 0.69) to 0.68 (95 CI, 0.66 to 0.70). CONCLUSIONS: These results indicate both the consistency and disparity of genetic effects on risk of MI between Hispanic and white populations. The improvement in the identified genetic markers on discrimination of MI in Hispanics was modest.
Authors: Anna Helgadottir; Gudmar Thorleifsson; Andrei Manolescu; Solveig Gretarsdottir; Thorarinn Blondal; Aslaug Jonasdottir; Adalbjorg Jonasdottir; Asgeir Sigurdsson; Adam Baker; Arnar Palsson; Gisli Masson; Daniel F Gudbjartsson; Kristinn P Magnusson; Karl Andersen; Allan I Levey; Valgerdur M Backman; Sigurborg Matthiasdottir; Thorbjorg Jonsdottir; Stefan Palsson; Helga Einarsdottir; Steinunn Gunnarsdottir; Arnaldur Gylfason; Viola Vaccarino; W Craig Hooper; Muredach P Reilly; Christopher B Granger; Harland Austin; Daniel J Rader; Svati H Shah; Arshed A Quyyumi; Jeffrey R Gulcher; Gudmundur Thorgeirsson; Unnur Thorsteinsdottir; Augustine Kong; Kari Stefansson Journal: Science Date: 2007-05-03 Impact factor: 47.728
Authors: Anna Helgadottir; Andrei Manolescu; Agnar Helgason; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Daniel F Gudbjartsson; Solveig Gretarsdottir; Kristinn P Magnusson; Gudmundur Gudmundsson; Andrew Hicks; Thorlakur Jonsson; Struan F A Grant; Jesus Sainz; Stephen J O'Brien; Sigurlaug Sveinbjornsdottir; Einar M Valdimarsson; Stefan E Matthiasson; Allan I Levey; Jerome L Abramson; Murdach P Reilly; Viola Vaccarino; Megan L Wolfe; Vilmundur Gudnason; Arshed A Quyyumi; Eric J Topol; Daniel J Rader; Gudmundur Thorgeirsson; Jeffrey R Gulcher; Hakon Hakonarson; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2005-11-10 Impact factor: 38.330
Authors: R B D'Agostino; G Burke; D O'Leary; M Rewers; J Selby; P J Savage; M F Saad; R N Bergman; G Howard; L Wagenknecht; S M Haffner Journal: Stroke Date: 1996-10 Impact factor: 7.914
Authors: Christopher A Haiman; Loïc Le Marchand; Jennifer Yamamato; Daniel O Stram; Xin Sheng; Laurence N Kolonel; Anna H Wu; David Reich; Brian E Henderson Journal: Nat Genet Date: 2007-07-08 Impact factor: 38.330
Authors: Nilesh J Samani; Jeanette Erdmann; Alistair S Hall; Christian Hengstenberg; Massimo Mangino; Bjoern Mayer; Richard J Dixon; Thomas Meitinger; Peter Braund; H-Erich Wichmann; Jennifer H Barrett; Inke R König; Suzanne E Stevens; Silke Szymczak; David-Alexandre Tregouet; Mark M Iles; Friedrich Pahlke; Helen Pollard; Wolfgang Lieb; Francois Cambien; Marcus Fischer; Willem Ouwehand; Stefan Blankenberg; Anthony J Balmforth; Andrea Baessler; Stephen G Ball; Tim M Strom; Ingrid Braenne; Christian Gieger; Panos Deloukas; Martin D Tobin; Andreas Ziegler; John R Thompson; Heribert Schunkert Journal: N Engl J Med Date: 2007-07-18 Impact factor: 91.245