02653nas a2200685   4500000000100000008004100001100001000042700001100052700000900063700000900072700000900081700001100090700001000101700000900111700001000120700001400130700001000144700001000154700001700164700001900181700001900200700001100219700000900230700001000239700001000249700001100259700001100270700001000281700000900291700001100300700001200311700001200323700001000335700001000345700001100355700001100366700000900377700000900386700001200395700001200407700001100419700001100430700001100441700001100452700001000463700001100473700001200484700001100496700000900507700001100516700001000527700001100537700001200548700001100560700001000571700001200581245006400593520129600657022001401953       2017                            d1 aLiu H1 aWang Z1 aLi Y1 aYu G1 aFu X1 aWang C1 aLiu W1 aYu Y1 aBao F1 aIrwanto A1 aLiu J1 aChu T1 aAndiappan AK1 aMaurer-Stroh S1 aLimviphuvadh V1 aWang H1 aMi Z1 aSun Y1 aSun L1 aWang L1 aWang C1 aYou J1 aLi J1 aFoo JN1 aLiany H1 aMeah WY1 aNiu G1 aYue Z1 aZhao Q1 aWang N1 aYu M1 aYu W1 aCheng X1 aKhor CC1 aSim KS1 aAung T1 aWang N1 aWang D1 aShi L1 aNing Y1 aZheng Z1 aYang R1 aLi J1 aYang J1 aYan L1 aShen J1 aZhang G1 aChen S1 aLiu J1 aZhang F00aGenome-wide Analysis of Protein-Coding Variants in Leprosy.3 a<p>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.</p>
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