In a genome-wide genetic study of early progression to active tuberculosis (TB), we genotyped 4,002 active TB cases and their household contacts in Lima, Peru. We first established TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases (h2g=0.212). We identified a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 x 10-8). With in silico and in vitro analyses we identified genetic variant rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

Early Progression to Active Tuberculosis is a Highly Heritable Trait Driven by 3q23 in Peruvians

Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

A positively selected FBN1 missense variant reduces height in Peruvian individuals