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

Nat Commun
Authors
Abstract

Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability ([Formula: see text]) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify 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 × 10). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

Year of Publication
2019
Journal
Nat Commun
Volume
10
Issue
1
Pages
3765
Date Published
2019 Aug 21
ISSN
2041-1723
DOI
10.1038/s41467-019-11664-1
PubMed ID
31434886
PubMed Central ID
PMC6704092
Links
Grant list
U01 HG009379 / HG / NHGRI NIH HHS / United States
U19 AI076217 / AI / NIAID NIH HHS / United States
U19 AI111224 / AI / NIAID NIH HHS / United States