OBJECTIVE: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether this GRS also predicts incident stroke. METHODS: Genotypes at nine CHD-relevant SNPs were determined in 494 cases of incident CHD, 320 cases of incident stroke and 1345 unaffected controls drawn from the population-based Greek component of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. An additive GRS was calculated for each study participant by adding one unit for the presence of each high-risk allele multiplied by the estimated effect size of that allele in the discovery samples. Statistical analysis was performed using logistic regression. RESULTS: The GRS was significantly associated with the incidence of CHD where the odds of CHD incidence in the highest quintile of the GRS were 1.74 times higher (95% confidence interval [CI]=1.25-2.43, p for trend=0.0004), compared to the lowest quintile. With respect to stroke, a weaker and non-significant positive association with GRS was apparent as the odds of stroke incidence in the highest quintile of the GRS were 1.36 times higher (95% CI=0.90-2.06, p for trend=0.188), compared to the lowest quintile. CONCLUSION: A GRS relying on nine documented "CHD-specific" SNPs is significantly predictive of CHD but it was not found to be statistically significantly associated with incident stroke.
OBJECTIVE: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether this GRS also predicts incident stroke. METHODS: Genotypes at nine CHD-relevant SNPs were determined in 494 cases of incident CHD, 320 cases of incident stroke and 1345 unaffected controls drawn from the population-based Greek component of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. An additive GRS was calculated for each study participant by adding one unit for the presence of each high-risk allele multiplied by the estimated effect size of that allele in the discovery samples. Statistical analysis was performed using logistic regression. RESULTS: The GRS was significantly associated with the incidence of CHD where the odds of CHD incidence in the highest quintile of the GRS were 1.74 times higher (95% confidence interval [CI]=1.25-2.43, p for trend=0.0004), compared to the lowest quintile. With respect to stroke, a weaker and non-significant positive association with GRS was apparent as the odds of stroke incidence in the highest quintile of the GRS were 1.36 times higher (95% CI=0.90-2.06, p for trend=0.188), compared to the lowest quintile. CONCLUSION: A GRS relying on nine documented "CHD-specific" SNPs is significantly predictive of CHD but it was not found to be statistically significantly associated with incident stroke.
Authors: S C Smith; S N Blair; R O Bonow; L M Brass; M D Cerqueira; K Dracup; V Fuster; A Gotto; S M Grundy; N H Miller; A Jacobs; D Jones; R M Krauss; L Mosca; I Ockene; R C Pasternak; T Pearson; M A Pfeffer; R D Starke; K A Taubert Journal: Circulation Date: 2001-09-25 Impact factor: 29.690
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; Gudmar Thorleifsson; Kristinn P Magnusson; Solveig Grétarsdottir; Valgerdur Steinthorsdottir; Andrei Manolescu; Gregory T Jones; Gabriel J E Rinkel; Jan D Blankensteijn; Antti Ronkainen; Juha E Jääskeläinen; Yoshiki Kyo; Guy M Lenk; Natzi Sakalihasan; Konstantinos Kostulas; Anders Gottsäter; Andrea Flex; Hreinn Stefansson; Torben Hansen; Gitte Andersen; Shantel Weinsheimer; Knut Borch-Johnsen; Torben Jorgensen; Svati H Shah; Arshed A Quyyumi; Christopher B Granger; Muredach P Reilly; Harland Austin; Allan I Levey; Viola Vaccarino; Ebba Palsdottir; G Bragi Walters; Thorbjorg Jonsdottir; Steinunn Snorradottir; Dana Magnusdottir; Gudmundur Gudmundsson; Robert E Ferrell; Sigurlaug Sveinbjornsdottir; Juha Hernesniemi; Mika Niemelä; Raymond Limet; Karl Andersen; Gunnar Sigurdsson; Rafn Benediktsson; Eric L G Verhoeven; Joep A W Teijink; Diederick E Grobbee; Daniel J Rader; David A Collier; Oluf Pedersen; Roberto Pola; Jan Hillert; Bengt Lindblad; Einar M Valdimarsson; Hulda B Magnadottir; Cisca Wijmenga; Gerard Tromp; Annette F Baas; Ynte M Ruigrok; Andre M van Rij; Helena Kuivaniemi; Janet T Powell; Stefan E Matthiasson; Jeffrey R Gulcher; Gudmundur Thorgeirsson; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2008-01-06 Impact factor: 38.330
Authors: Nina P Paynter; Daniel I Chasman; Guillaume Paré; Julie E Buring; Nancy R Cook; Joseph P Miletich; Paul M Ridker Journal: JAMA Date: 2010-02-17 Impact factor: 56.272
Authors: Ruth McPherson; Alexander Pertsemlidis; Nihan Kavaslar; Alexandre Stewart; Robert Roberts; David R Cox; David A Hinds; Len A Pennacchio; Anne Tybjaerg-Hansen; Aaron R Folsom; Eric Boerwinkle; Helen H Hobbs; Jonathan C Cohen Journal: Science Date: 2007-05-03 Impact factor: 47.728
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
Authors: Carla A Ibrahim-Verbaas; Myriam Fornage; Joshua C Bis; Seung Hoan Choi; Bruce M Psaty; James B Meigs; Madhu Rao; Mike Nalls; Joao D Fontes; Christopher J O'Donnell; Sekar Kathiresan; Georg B Ehret; Caroline S Fox; Rainer Malik; Martin Dichgans; Helena Schmidt; Jari Lahti; Susan R Heckbert; Thomas Lumley; Kenneth Rice; Jerome I Rotter; Kent D Taylor; Aaron R Folsom; Eric Boerwinkle; Wayne D Rosamond; Eyal Shahar; Rebecca F Gottesman; Peter J Koudstaal; Najaf Amin; Renske G Wieberdink; Abbas Dehghan; Albert Hofman; André G Uitterlinden; Anita L Destefano; Stephanie Debette; Luting Xue; Alexa Beiser; Philip A Wolf; Charles Decarli; M Arfan Ikram; Sudha Seshadri; Thomas H Mosley; W T Longstreth; Cornelia M van Duijn; Lenore J Launer Journal: Stroke Date: 2014-01-16 Impact factor: 7.914