Using human genetics to understand the causes and consequences of circulating cardiac troponin I in the general population

Abstract

Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of highsensitivity cTnI concentrations with 48 115 individuals.We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes:CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1andLMAN1. Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction, but could not rule out a causal role for cTnI in heart failure. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population.