Genome-Wide Analysis of Protein-Coding Variants in Leprosy

被引：37

作者：

Liu, Hong ^{[1
,2
,3
,4
]}

Wang, Zhenzhen ^{[1
,2
,3
]}

Li, Yi ^{[5
,6
]}

Yu, Gongqi ^{[1
,3
]}

Fu, Xi'an ^{[1
,3
,7
]}

Wang, Chuan ^{[1
,3
]}

Liu, Wenting ^{[5
]}

Yu, Yongxiang ^{[1
,2
]}

Bao, Fangfang ^{[1
,3
]}

Irwanto, Astrid ^{[5
]}

Liu, Jian ^{[1
,2
]}

Chu, Tongsheng ^{[1
,2
]}

Andiappan, Anand Kumar ^{[8
]}

Maurer-Stroh, Sebastian ^{[9
,10
]}

Limviphuvadh, Vachiranee ^{[9
]}

Wang, Honglei ^{[1
,3
,7
]}

Mi, Zihao ^{[1
,3
]}

Sun, Yonghu ^{[1
,3
]}

Sun, Lele ^{[1
,3
]}

Wang, Ling ^{[5
]}

Wang, Chaolong ^{[11
]}

You, Jiabao ^{[1
,2
]}

Li, Jinghui ^{[1
,2
]}

Foo, Jia Nee ^{[5
]}

Liany, Herty ^{[5
]}

Meah, Wee Yang ^{[5
]}

Niu, Guiye ^{[1
,2
,3
]}

Yue, Zhenhua ^{[1
,3
,7
]}

Zhao, Qing ^{[1
,3
,7
]}

Wang, Na ^{[1
,3
,7
]}

Yu, Meiwen ^{[12
,13
]}

Yu, Wenjun ^{[1
,3
,14
]}

Cheng, Xiujun ^{[1
,3
,7
]}

Khor, Chiea Chuen ^{[5
]}

Sim, Kar Seng ^{[5
]}

Aung, Tin ^{[15
]}

Wang, Ningli ^{[16
]}

Wang, Deyun ^{[17
]}

Shi, Li ^{[18
]}

Ning, Yong ^{[19
]}

Zheng, Zhongyi ^{[20
]}

Yang, Rongde ^{[21
]}

Li, Jinlan ^{[22
]}

Yang, Jun ^{[23
]}

Yan, Liangbin ^{[12
,13
]}

Shen, Jianping ^{[12
,13
]}

Zhang, Guocheng ^{[12
,13
]}

Chen, Shumin ^{[1
,2
]}

Liu, Jianjun ^{[5
]}

Zhang, Furen ^{[1
,2
,3
,4
,14
,24
]}

机构：

[1] Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan, Shandong, Peoples R China

[2] Shandong Univ, Shandong Prov Hosp Skin Dis, Jinan, Shandong, Peoples R China

[3] Shandong Prov Key Lab Dermatovenereol, Jinan, Shandong, Peoples R China

[4] Shandong Prov Med Ctr Dermatovenereol, Jinan, Shandong, Peoples R China

[5] ASTAR, Genome Inst Singapore, Human Genet, Singapore, Singapore

[6] Jackson Lab, Computat Sci, Farmington, CT USA

[7] Shandong Univ, Sch Med, Jinan, Shandong, Peoples R China

[8] Agcy Sci Technol & Res Singapore, Singapore Immunol Network, Singapore, Singapore

[9] ASTAR, Bioinformat Inst, Biomol Funct Discovery Div, Singapore, Singapore

[10] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore

[11] ASTAR, Genome Inst Singapore, Computat & Syst Biol, Singapore, Singapore

[12] Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China

[13] Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China

[14] Univ Jinan, Shandong Acad Med Sci, Sch Med & Life Sci, Jinan, Shandong, Peoples R China

[15] Singapore Natl Eye Ctr, Glaucoma Dept, Singapore, Singapore

[16] Capital Med Univ, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Tongren Eye Ctr, Beijing, Peoples R China

[17] Natl Univ Singapore, Dept Otolaryngol, Singapore, Singapore

[18] Shandong Univ, Affiliated Hosp 2, Dept Otolaryngol, Jinan, Shandong, Peoples R China

[19] Sichuan Prov Inst Dermatol, Chengdu, Sichuan, Peoples R China

[20] Honghe Inst Dermatol, Honghe, Yunnan, Peoples R China

[21] Wenshan Inst Dermatol, Wenshan, Yunnan, Peoples R China

[22] Guizhou Prov Ctr Dis Control & Prevent, Guiyang, Guizhou, Peoples R China

[23] Yunnan Prov Ctr Dis Control & Prevent, Kunming, Yunnan, Peoples R China

[24] Natl Clin Key Project Dermatol & Venereol, Jinan, Shandong, Peoples R China

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2017年 / 137卷 / 12期

基金：

中国国家自然科学基金;

关键词：

SUSCEPTIBILITY LOCI; ASSOCIATION; RARE; FILAGGRIN; IDENTIFICATION; EXPRESSION; COMMON;

D O I：

10.1016/j.jid.2017.08.004

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding 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 Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1.71 x 10(-9), odds ratio [OR] = 4.35) and rs149308743 in CARD9 (P = 2.09 x 10(-8), OR = 4.75); three low-frequency variants: rs76418789 in IL23R (P = 1.03 x 10(-10), OR = 1.36), rs146466242 in FLG (P = 3.39 x 10(-12), OR = 1.45), and rs55882956 in TYK2 (P = 1.04 x 10(-6), OR = 1.30); and two common variants: rs780668 in SLC29A3 (P = 2.17 x 10(-9), OR = 1.14) and rs181206 in IL27 (P = 1.08 x 10(-7), OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, showed involvement of skin barrier and endocytosis/phagocytosis/autophagy, in addition to known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein-coding variant studies for complex diseases.

引用

页码：2544 / 2551

页数：8

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