BACKGROUND: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque. METHODS: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model. RESULTS: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR = 1.32, 95% confidence interval: 1.17, 1.49, P = 1.08 × 10(-5)), but not in the other populations (P = 0.90 in EA and P = 0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR = 1.07, P = 0.02) and in AI (OR = 1.10, P = 0.05). CONCLUSIONS: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries.
BACKGROUND: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque. METHODS: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model. RESULTS: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR = 1.32, 95% confidence interval: 1.17, 1.49, P = 1.08 × 10(-5)), but not in the other populations (P = 0.90 in EA and P = 0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR = 1.07, P = 0.02) and in AI (OR = 1.10, P = 0.05). CONCLUSIONS: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries.
Authors: Kari E North; Barbara V Howard; Thomas K Welty; Lyle G Best; Elisa T Lee; J L Yeh; Richard R Fabsitz; Mary J Roman; Jean W MacCluer Journal: Am J Epidemiol Date: 2003-02-15 Impact factor: 4.897
Authors: E T Lee; T K Welty; R Fabsitz; L D Cowan; N A Le; A J Oopik; A J Cucchiara; P J Savage; B V Howard Journal: Am J Epidemiol Date: 1990-12 Impact factor: 4.897
Authors: Helaine E Resnick; Robert S Lindsay; Mary McGrae McDermott; Richard B Devereux; Kristina L Jones; Richard R Fabsitz; Barbara V Howard Journal: Circulation Date: 2004-02-17 Impact factor: 29.690
Authors: D H O'Leary; J F Polak; S K Wolfson; M G Bond; W Bommer; S Sheth; B M Psaty; A R Sharrett; T A Manolio Journal: Stroke Date: 1991-09 Impact factor: 7.914
Authors: M J Roman; P S Saba; R Pini; M Spitzer; T G Pickering; S Rosen; M H Alderman; R B Devereux Journal: Circulation Date: 1992-12 Impact factor: 29.690
Authors: Sekar Kathiresan; Olle Melander; Candace Guiducci; Aarti Surti; Noël P Burtt; Mark J Rieder; Gregory M Cooper; Charlotta Roos; Benjamin F Voight; Aki S Havulinna; Björn Wahlstrand; Thomas Hedner; Dolores Corella; E Shyong Tai; Jose M Ordovas; Göran Berglund; Erkki Vartiainen; Pekka Jousilahti; Bo Hedblad; Marja-Riitta Taskinen; Christopher Newton-Cheh; Veikko Salomaa; Leena Peltonen; Leif Groop; David M Altshuler; Marju Orho-Melander Journal: Nat Genet Date: 2008-01-13 Impact factor: 38.330
Authors: D H O'Leary; J F Polak; R A Kronmal; S J Kittner; M G Bond; S K Wolfson; W Bommer; T R Price; J M Gardin; P J Savage Journal: Stroke Date: 1992-12 Impact factor: 7.914
Authors: Cristina Alonso-Bouzón; Laure Carcaillon; Francisco J García-García; María S Amor-Andrés; Mariam El Assar; Leocadio Rodríguez-Mañas Journal: Age (Dordr) Date: 2014-02
Authors: Aditi Shendre; Marguerite R Irvin; Bradley E Aouizerat; Howard W Wiener; Ana I Vazquez; Kathryn Anastos; Jason Lazar; Chenglong Liu; Roksana Karim; Nita A Limdi; Mardge H Cohen; Elizabeth T Golub; Degui Zhi; Robert C Kaplan; Sadeep Shrestha Journal: Atherosclerosis Date: 2014-01-30 Impact factor: 5.162
Authors: Stephanie A Bien; Genevieve L Wojcik; Chani J Hodonsky; Christopher R Gignoux; Iona Cheng; Tara C Matise; Ulrike Peters; Eimear E Kenny; Kari E North Journal: Annu Rev Genomics Hum Genet Date: 2019-04-12 Impact factor: 8.929
Authors: Jose D Vargas; Ani Manichaikul; Xin-Qun Wang; Stephen S Rich; Jerome I Rotter; Wendy S Post; Joseph F Polak; Matthew J Budoff; David A Bluemke Journal: Atherosclerosis Date: 2015-12-08 Impact factor: 5.162
Authors: Ivan Zivotić; Tamara Djurić; Aleksandra Stanković; Ana Djordjević; Igor Končar; Lazar Davidović; Dragan Alavantić; Maja Zivković Journal: Exp Biol Med (Maywood) Date: 2016-03-03
Authors: Rector Arya; Agustin Escalante; Vidya S Farook; Jose F Restrepo; Daniel F Battafarano; Marcio Almeida; Mark Z Kos; Marcel J Fourcaudot; Srinivas Mummidi; Satish Kumar; Joanne E Curran; Christopher P Jenkinson; John Blangero; Ravindranath Duggirala; Inmaculada Del Rincon Journal: Atherosclerosis Date: 2017-11-26 Impact factor: 5.162
Authors: Pradeep Natarajan; Joshua C Bis; Lawrence F Bielak; Amanda J Cox; Marcus Dörr; Mary F Feitosa; Nora Franceschini; Xiuqing Guo; Shih-Jen Hwang; Aaron Isaacs; Min A Jhun; Maryam Kavousi; Ruifang Li-Gao; Leo-Pekka Lyytikäinen; Riccardo E Marioni; Ulf Schminke; Nathan O Stitziel; Hayato Tada; Jessica van Setten; Albert V Smith; Dina Vojinovic; Lisa R Yanek; Jie Yao; Laura M Yerges-Armstrong; Najaf Amin; Usman Baber; Ingrid B Borecki; J Jeffrey Carr; Yii-Der Ida Chen; L Adrienne Cupples; Pim A de Jong; Harry de Koning; Bob D de Vos; Ayse Demirkan; Valentin Fuster; Oscar H Franco; Mark O Goodarzi; Tamara B Harris; Susan R Heckbert; Gerardo Heiss; Udo Hoffmann; Albert Hofman; Ivana Išgum; J Wouter Jukema; Mika Kähönen; Sharon L R Kardia; Brian G Kral; Lenore J Launer; Joe Massaro; Roxana Mehran; Braxton D Mitchell; Thomas H Mosley; Renée de Mutsert; Anne B Newman; Khanh-Dung Nguyen; Kari E North; Jeffrey R O'Connell; Matthijs Oudkerk; James S Pankow; Gina M Peloso; Wendy Post; Michael A Province; Laura M Raffield; Olli T Raitakari; Dermot F Reilly; Fernando Rivadeneira; Frits Rosendaal; Samantha Sartori; Kent D Taylor; Alexander Teumer; Stella Trompet; Stephen T Turner; Andre G Uitterlinden; Dhananjay Vaidya; Aad van der Lugt; Uwe Völker; Joanna M Wardlaw; Christina L Wassel; Stefan Weiss; Mary K Wojczynski; Diane M Becker; Lewis C Becker; Eric Boerwinkle; Donald W Bowden; Ian J Deary; Abbas Dehghan; Stephan B Felix; Vilmundur Gudnason; Terho Lehtimäki; Rasika Mathias; Dennis O Mook-Kanamori; Bruce M Psaty; Daniel J Rader; Jerome I Rotter; James G Wilson; Cornelia M van Duijn; Henry Völzke; Sekar Kathiresan; Patricia A Peyser; Christopher J O'Donnell Journal: Circ Cardiovasc Genet Date: 2016-11-21