Genome-wide Analysis of Protein-Coding Variants in Leprosy

Published date : 22 Aug 2017

Although genome-wide association studies (GWAS) have greatly advanced our understanding on the contribution of common non-coding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in 7,048 leprosy patients and 14,398 healthy controls of Han Chinese. Seven to our knowledge previously unreported coding variants at exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1.71 × 10-9, odds ratio (OR) = 4.35) and rs149308743 in CARD9 (P = 2.09 × 10-8, OR = 4.75); three low frequency variants: rs76418789 in IL23R (P = 1.03 × 10-10, OR = 1.36), rs146466242 in FLG (P = 3.39 × 10-12, OR = 1.45), and rs55882956 in TYK2 (P = 1.04 × 10-6, OR = 1.30); and two common variants: rs780668 in SLC29A3 (P = 2.17 × 10-9, OR = 1.14) and rs181206 in IL27 (P = 1.08 × 10-7, OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, revealed involvement of skin barrier and endocytosis/phagocytosis/autophagy, besides known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein coding variant studies for complex diseases.

type
Journal Paper
journal
Journal of Investigative Dermatology, 2017, Aug 22, doi: 10.1016/j.jid.2017.08.004
pubmed
28842327
Url
http://www.jidonline.org/article/S0022-202X(17)32793-8/pdf
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6.287