Genome-wide association study of coronary artery disease in the Japanese
Open Access
- 5 October 2011
- journal article
- research article
- Published by Springer Nature in European Journal of Human Genetics
- Vol. 20 (3) , 333-340
- https://doi.org/10.1038/ejhg.2011.184
Abstract
A new understanding of the genetic basis of coronary artery disease (CAD) has recently emerged from genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs), thus far performed mostly in European-descent populations. To identify novel susceptibility gene variants for CAD and confirm those previously identified mostly in populations of European descent, a multistage GWA study was performed in the Japanese. In the discovery phase, we first genotyped 806 cases and 1337 controls with 451 382 SNP markers and subsequently assessed 34 selected SNPs with direct genotyping (541 additional cases) and in silico comparison (964 healthy controls). In the replication phase, involving 3052 cases and 6335 controls, 12 SNPs were tested; CAD association was replicated and/or verified for 4 (of 12) SNPs from 3 loci: near BRAP and ALDH2 on 12q24 (P=1.6 × 10−34), HLA-DQB1 on 6p21 (P=4.7 × 10−7), and CDKN2A/B on 9p21 (P=6.1 × 10−16). On 12q24, we identified the strongest association signal with the strength of association substantially pronounced for a subgroup of myocardial infarction cases (P=1.4 × 10−40). On 6p21, an HLA allele, DQB1*0604, could show one of the most prominent association signals in an ∼ 8-Mb interval that encompasses the LTA gene, where an association with myocardial infarction had been reported in another Japanese study. CAD association was also identified at CDKN2A/B, as previously reported in different populations of European descent and Asians. Thus, three loci confirmed in the Japanese GWA study highlight the likely presence of risk alleles with two types of genetic effects – population specific and common – on susceptibility to CAD.Keywords
This publication has 36 references indexed in Scilit:
- Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east AsiansNature Genetics, 2011
- A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery diseaseNature Genetics, 2011
- Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studiesThe Lancet, 2011
- Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studiesNature Genetics, 2006
- DNA repair capacity measured by high throughput alkaline comet assays in EBV-transformed cell lines and peripheral blood cells from cancer patients and healthy volunteersMutation Research - Genetic Toxicology and Environmental Mutagenesis, 2005
- Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-α secretion in vitroNature, 2004
- Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarctionNature Genetics, 2002
- Aldehyde Dehydrogenase 2 Gene Is a Risk Factor for Myocardial Infarction in Japanese Men.Hypertension Research, 2002
- Genomic Control for Association StudiesBiometrics, 1999
- A Low Prevalence of Coronary Heart Disease among Subjects with Increased High-Density Lipoprotein Cholesterol Levels, Including Those with Plasma Cholesteryl Ester Transfer Protein DeficiencyPreventive Medicine, 1998