Large-scale association analysis identifies new risk loci for coronary artery disease

Abstract

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

“…We also examined the associations of the IGF‐I‐ and IGFBP‐3‐associated SNPs with anthropometric traits (height, BMI, waist‐to‐hip ratio, and fat percentage) (Heid et al ., 2010; Lango Allen et al ., 2010; Speliotes et al ., 2010), bone mineral density (Estrada et al ., 2012), risk of type 2 diabetes (Voight et al ., 2010; Morris et al ., 2012) and related traits (fasting glucose, 2‐h glucose, HbA1c, fasting insulin, proinsulin, HOMA‐IR, and HOMA‐B) (Dupuis et al ., 2010; Saxena et al ., 2010; Soranzo et al ., 2010), and coronary artery disease (Coronary Artery Disease Genetics C, 2011; Schunkert et al ., 2011; Consortium CAD and Deloukas, 2013) (Table S9, Supporting information). Many nominal associations were expected because of the known influence of the IGF system on these traits.…”

“…Top SNPs associated with levels of IGF‐I and IGFBP‐3 were examined in relationship to other phenotypes using published data on serum metabolites (Suhre et al ., 2011; Shin et al ., 2014), anthropometric traits (Heid et al ., 2010; Lango Allen et al ., 2010; Speliotes et al ., 2010), bone mineral density (Estrada et al ., 2012), diabetes (Voight et al ., 2010; Morris et al ., 2012) and glycemic traits (Dupuis et al ., 2010; Saxena et al ., 2010; Soranzo et al ., 2010), coronary artery disease (Coronary Artery Disease Genetics C, 2011; Schunkert et al ., 2011; Consortium CAD and Deloukas, 2013), and survival beyond 90 years (Broer et al ., 2015). Detailed information of the published datasets used including its references is given in Table S9 (Supporting information).…”

Lipoprotein(a) Interactions With Low‐Density Lipoprotein Cholesterol and Other Cardiovascular Risk Factors in Premature Acute Coronary Syndrome (ACS)

“…High Lp(a) has been determined as the strongest independent genetic risk factor of CV disease,27, 28 and a causal role for circulating Lp(a) in cardiovascular events has been demonstrated by Mendelian randomization 2. Lp(a) has also been shown to be a potential causal factor for valve calcification and aortic stenosis in a large genome‐wide association study,3 and in several subsequent reports 29, 30.…”

The interplay of LncRNA ANRIL and miR‐181b on the inflammation‐relevant coronary artery disease through mediating NF‐κB signalling pathway

“…Coronary artery disease, one principal cause for heart disease‐induced death, has been on the rise in its prevalence because of increased populations with obesity and diabetes 19, 20, 21. Currently, the treatments for CAD mainly incorporated chemotherapy, percutaneous coronary intervention, coronary artery bypass grafting and so on, it still brought about high mortality 22.…”