Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/ncomms7793
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Funding
- Key Program of the National Natural Science Foundation of China [81130031]
- National Science Fund for Excellent Young Scholars [81222022]
- Outstanding Talents of Organization Department of the CPC (Communist Party of China) Central Committee program
- Local Universities Characteristics and Advantages of Discipline Development Program of the Ministry of Finance of China
- National Natural Science Foundation of China [81072461, 31000528, 81000692, 81071285, 81172866, 81172591, 81370044, 31200939]
- New Century Excellent Talents in University [NCET-11-0889]
- Pre-National Basic Research Program of China (973 Plan) [2012CB722404]
- Program for Outstanding Talents of Anhui Medical University
- Anhui Province Natural Science Foundation Program [1508085JGD05]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT-1046]
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Genome-wide association studies (GWASs) have reproducibly associated similar to 40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 x 10(-08)). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.
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