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Genome-wide Analysis of Protein-Coding Variants in Leprosy.

Abstract

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.

More information

Type
Journal Article
Author
Liu H
Wang Z
Li Y
Yu G
Fu X
Wang C
Liu W
Yu Y
Bao F
Irwanto A
Liu J
Chu T
Andiappan AK
Maurer-Stroh S
Limviphuvadh V
Wang H
Mi Z
Sun Y
Sun L
Wang L
Wang C
You J
Li J
Foo JN
Liany H
Meah WY
Niu G
Yue Z
Zhao Q
Wang N
Yu M
Yu W
Cheng X
Khor CC
Sim KS
Aung T
Wang N
Wang D
Shi L
Ning Y
Zheng Z
Yang R
Li J
Yang J
Yan L
Shen J
Zhang G
Chen S
Liu J
Zhang F

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