rs16986953 is a SNP identified by a genome-wide association study for coronary artery disease. Coronary artery disease (CAD) is one of the most common causes of death worldwide. A significant proportion of risk for CAD has been shown to be heritable, leading to many efforts to understand the genetic underpinnings of the disease. The SNP rs16986953 is located on chromosome 2. It is located in a gene desert and is located 1.3 Mb away from the APOB gene. The nearest transcript is AK097927. Mouse model knockouts of APOB display a relevant cardiovascular phenotype. Homozygous mice can often die midgestation and longer survivors can exhibit exencephaly. Heterozygous mice show reduced plasmid cholesterol and apolipoprotein levels [PMID 9502790
] [PMID 8692825] [PMID 10893242]. However, this SNP has not yet been functionally linked to the APOB gene.
This SNP was identified in an association study with 63,746 CAD cases and 130,681 controls. Data was obtained through the CARDIoGRAMplusC4D Consortium as a meta-analysis of several different genome-wide association studies. This study included individuals of European or South Asian descent.
rs16986953 is associated with coronary artery disease in males (p=1.89e-8) and young CAD cases (1.67e-8). Young CAD cases are defined as individuals less than 50 years of age. Its overall association with CAD is (p=0.0000867). This was the only SNP significantly associated with CAD as identified in a sub-group. Further interaction analyses in a subset of studies with individual-level data found evidence of association with age (p=0.033), but not with sex (p=0.708) so further studies are needed to confirm the finding.
The reference allele of rs12621411 is A with the risk allele being a G. The effect allele frequency is 0.08878. This SNP has a proxy SNP (rs12621411) in LD with r^2=0.85 with minor allele C and minor allele A, which was used because rs16986953 was not genotyped in HapMap. For males the odds ratio is 1.11 as compared to 1.03 for females. For young individuals, the odds ratio is 1.17 as opposed to 1.11 for old individuals.
[23202125?dopt=Abstract PMID 23202125] The CARDIoGRAMplusC4D Consortium, Deloukas P, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nature Genetics. 45(25-33). 2013.
] [PMID 8692825
