BACKGROUND: Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. METHODS: The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. RESULTS: The association previously observed on chromosome 9p21 was independently replicated (p=3.08e-07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. CONCLUSION: A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors.
BACKGROUND: Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. METHODS: The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. RESULTS: The association previously observed on chromosome 9p21 was independently replicated (p=3.08e-07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. CONCLUSION: A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors.
Entities:
Keywords:
Asian and Caucasian populations; Coronary artery disease; common causal mutation; genetics; genome-wide association study; myocardial infarction; population studies
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: Themistocles L Assimes; Joshua W Knowles; Analabha Basu; Carlos Iribarren; Audrey Southwick; Hua Tang; Devin Absher; Jun Li; Joan M Fair; Geoffrey D Rubin; Stephen Sidney; Stephen P Fortmann; Alan S Go; Mark A Hlatky; Richard M Myers; Neil Risch; Thomas Quertermous Journal: Hum Mol Genet Date: 2008-04-28 Impact factor: 6.150