NEW YORK – A new study has unearthed a dozen variants with apparent ties to heart failure risk, including SNPs at 10 sites not linked to the condition in the past.
Results from the genome-wide association meta-analysis, appearing online today in Nature Communications, are expected to "extend our knowledge of the pathways underlying [heart failure] and may inform new therapeutic strategies," senior author Thomas Lumbers, a researcher affiliated with the University College London and St. Bartholomew's Hospital Bart's Heart Centre, and his colleagues wrote.
Lumbers and colleagues from the UK, Australia, the US, and elsewhere brought together data for almost 1 million individuals with or without heart failure, focusing in on 12 variants at 11 loci that coincided with the heart failure cases. They also attempted to tease out variants associated with underlying heart failure causes — from atrial fibrillation to coronary artery disease — which highlighted risk loci in and around genes from pathways contributing to cardiac development and other processes.
"We speculate that future analysis of [heart failure] subtypes may yield additional insights into the genetic architecture of [heart failure] to inform new approaches to prevention and treatment," the authors wrote.
For the meta-analysis, the team considered genotyping profiles generated with high-density arrays and imputation in 47,309 individuals of European descent with heart failure and 930,014 without, enrolled through more than two dozen prior analyses by members of the "Heart Failure Molecular Epidemiology for Therapeutic Targets" consortium.
Based on data spanning more than 8.2 million common and less frequent variants, the researchers narrowed in on 12 heart failure-associated SNPs at 11 loci. From there, they incorporated tissue-specific gene expression and other data to take a look at the potential regulatory and functional effects of these apparent risk SNPs, along with their pleiotropic effects.
In a series of secondary analyses, the team tapped into the genes and pathways that were overrepresented in the heart failure group, considered causal contributors to heart failure, and looked at linkage disequilibrium and heritability patterns for the heart failure-associated SNPs.
Meanwhile, the team's conditional analyses indicated that genetic contributors to other risk factors such as atrial fibrillation, body mass index (BMI), high blood pressure, or blood triglyceride levels may have independent causal contributions to heart failure. In contrast, the heart failure risk related to type 2 diabetes seemed to rely on its ties to coronary artery disease.
Overall, though, the authors noted that the large GWAS led to a "modest" set of heart failure contributors relative to association studies focused on specific heart conditions, including atrial fibrillation, "suggesting that an important component of [heart failure] heritability may be more attributable to specific disease subtypes than components of a final common pathway."