Genome-Wide Analysis of Protein-Coding Variants in Leprosy

Hong Liu; Zhenzhen Wang; Yi Li; Gongqi Yu; Xi'an Fu; Chuan Wang; Wenting Liu; Yongxiang Yu; Fangfang Bao; Astrid Irwanto; Jian Liu; Tongsheng Chu; Anand Kumar Andiappan; Sebastian Maurer-Stroh; Vachiranee Limviphuvadh; Honglei Wang; Zihao Mi; Yonghu Sun; Lele Sun; Ling Wang; Chaolong Wang; Jiabao You; Jinghui Li; Jia Nee Foo; Herty Liany; Wee Yang Meah; Guiye Niu; Zhenhua Yue; Qing Zhao; Na Wang; Meiwen Yu; Wenjun Yu; Xiujun Cheng; Chiea Chuen Khor; Kar Seng Sim; Tin Aung; Ningli Wang; Deyun Wang; Li Shi; Yong Ning; Zhongyi Zheng; Rongde Yang; Jinlan Li; Jun Yang; Liangbin Yan; Jianping Shen; Guocheng Zhang; Shumin Chen; Jianjun Liu; Furen Zhang

doi:10.1016/j.jid.2017.08.004

Genome-Wide Analysis of Protein-Coding Variants in Leprosy

Hong Liu, Zhenzhen Wang, Yi Li, Gongqi Yu, Xi'an Fu, Chuan Wang, Wenting Liu, Yongxiang Yu, Fangfang Bao, Astrid Irwanto, Jian Liu, Tongsheng Chu, Anand Kumar Andiappan, Sebastian Maurer-Stroh, Vachiranee Limviphuvadh, Honglei Wang, Zihao Mi, Yonghu Sun, Lele Sun, Ling WangChaolong Wang, Jiabao You, Jinghui Li, Jia Nee Foo, Herty Liany, Wee Yang Meah, Guiye Niu, Zhenhua Yue, Qing Zhao, Na Wang, Meiwen Yu, Wenjun Yu, Xiujun Cheng, Chiea Chuen Khor, Kar Seng Sim, Tin Aung, Ningli Wang, Deyun Wang, Li Shi, Yong Ning, Zhongyi Zheng, Rongde Yang, Jinlan Li, Jun Yang, Liangbin Yan, Jianping Shen, Guocheng Zhang, Shumin Chen, Jianjun Liu, Furen Zhang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

Abstract

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 × 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, 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.

Original language	English
Pages (from-to)	2544-2551
Number of pages	8
Journal	Journal of Investigative Dermatology
Volume	137
Issue number	12
DOIs	https://doi.org/10.1016/j.jid.2017.08.004
Publication status	Published - Dec 2017
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2017 The Authors

ASJC Scopus Subject Areas

Biochemistry
Molecular Biology
Dermatology
Cell Biology

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10.1016/j.jid.2017.08.004

Cite this

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, A. K., Maurer-Stroh, S., Limviphuvadh, V., Wang, H., Mi, Z., Sun, Y., Sun, L., ... Zhang, F. (2017). Genome-Wide Analysis of Protein-Coding Variants in Leprosy. Journal of Investigative Dermatology, 137(12), 2544-2551. https://doi.org/10.1016/j.jid.2017.08.004

@article{3ee632ca0b5448a9a86efeeb57c321d6,

title = "Genome-Wide Analysis of Protein-Coding Variants in Leprosy",

abstract = "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 × 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, 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.",

author = "Hong Liu and Zhenzhen Wang and Yi Li and Gongqi Yu and Xi'an Fu and Chuan Wang and Wenting Liu and Yongxiang Yu and Fangfang Bao and Astrid Irwanto and Jian Liu and Tongsheng Chu and Andiappan, \{Anand Kumar\} and Sebastian Maurer-Stroh and Vachiranee Limviphuvadh and Honglei Wang and Zihao Mi and Yonghu Sun and Lele Sun and Ling Wang and Chaolong Wang and Jiabao You and Jinghui Li and Foo, \{Jia Nee\} and Herty Liany and Meah, \{Wee Yang\} and Guiye Niu and Zhenhua Yue and Qing Zhao and Na Wang and Meiwen Yu and Wenjun Yu and Xiujun Cheng and Khor, \{Chiea Chuen\} and Sim, \{Kar Seng\} and Tin Aung and Ningli Wang and Deyun Wang and Li Shi and Yong Ning and Zhongyi Zheng and Rongde Yang and Jinlan Li and Jun Yang and Liangbin Yan and Jianping Shen and Guocheng Zhang and Shumin Chen and Jianjun Liu and Furen Zhang",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = dec,

doi = "10.1016/j.jid.2017.08.004",

language = "English",

volume = "137",

pages = "2544--2551",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Nature Publishing Group",

number = "12",

}

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 2017, 'Genome-Wide Analysis of Protein-Coding Variants in Leprosy', Journal of Investigative Dermatology, vol. 137, no. 12, pp. 2544-2551. https://doi.org/10.1016/j.jid.2017.08.004

TY - JOUR

T1 - Genome-Wide Analysis of Protein-Coding Variants in Leprosy

AU - Liu, Hong

AU - Wang, Zhenzhen

AU - Li, Yi

AU - Yu, Gongqi

AU - Fu, Xi'an

AU - Wang, Chuan

AU - Liu, Wenting

AU - Yu, Yongxiang

AU - Bao, Fangfang

AU - Irwanto, Astrid

AU - Liu, Jian

AU - Chu, Tongsheng

AU - Andiappan, Anand Kumar

AU - Maurer-Stroh, Sebastian

AU - Limviphuvadh, Vachiranee

AU - Wang, Honglei

AU - Mi, Zihao

AU - Sun, Yonghu

AU - Sun, Lele

AU - Wang, Ling

AU - Wang, Chaolong

AU - You, Jiabao

AU - Li, Jinghui

AU - Foo, Jia Nee

AU - Liany, Herty

AU - Meah, Wee Yang

AU - Niu, Guiye

AU - Yue, Zhenhua

AU - Zhao, Qing

AU - Wang, Na

AU - Yu, Meiwen

AU - Yu, Wenjun

AU - Cheng, Xiujun

AU - Khor, Chiea Chuen

AU - Sim, Kar Seng

AU - Aung, Tin

AU - Wang, Ningli

AU - Wang, Deyun

AU - Shi, Li

AU - Ning, Yong

AU - Zheng, Zhongyi

AU - Yang, Rongde

AU - Li, Jinlan

AU - Yang, Jun

AU - Yan, Liangbin

AU - Shen, Jianping

AU - Zhang, Guocheng

AU - Chen, Shumin

AU - Liu, Jianjun

AU - Zhang, Furen

PY - 2017/12

Y1 - 2017/12

N2 - 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 × 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, 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.

AB - 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 × 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, 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.

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M3 - Article

C2 - 28842327

AN - SCOPUS:85035072740

SN - 0022-202X

VL - 137

SP - 2544

EP - 2551

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 12

ER -

Genome-Wide Analysis of Protein-Coding Variants in Leprosy

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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