Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis

被引：71

作者：

Benyamin, Beben ^{[1
,2
]}

He, Ji ^{[3
]}

Zhao, Qiongyi ^{[1
]}

Gratten, Jacob ^{[1
,2
]}

Garton, Fleur ^{[1
,2
]}

Leo, Paul J. ^{[4
,5
]}

Liu, Zhijun ^{[1
,2
]}

Mangelsdorf, Marie ^{[1
]}

Al-Chalabi, Ammar ^{[6
]}

Anderson, Lisa ^{[4
,5
]}

Butler, Timothy J. ^{[1
]}

Chen, Lu ^{[3
]}

Chen, Xiang-Ding ^{[7
,8
]}

Cremin, Katie ^{[4
,5
]}

Deng, Hong-Weng ^{[9
]}

Devine, Matthew ^{[10
]}

Edson, Janette ^{[1
]}

Fifita, Jennifer A. ^{[11
]}

Furlong, Sarah ^{[1
]}

Han, Ying-Ying ^{[12
]}

Harris, Jessica ^{[4
,12
]}

Henders, Anjali K. ^{[1
,2
]}

Jeffree, Rosalind L. ^{[13
]}

Jin, Zi-Bing ^{[14
]}

Li, Zhongshan ^{[15
]}

Li, Ting ^{[16
]}

Li, Mengmeng ^{[16
]}

Lin, Yong ^{[12
]}

Liu, Xiaolu ^{[3
]}

Marshall, Mhairi ^{[4
,5
]}

McCann, Emily P. ^{[11
]}

Mowry, Bryan J. ^{[1
]}

Ngo, Shyuan T. ^{[1
,17
]}

Pamphlett, Roger ^{[18
]}

Ran, Shu ^{[12
]}

Reutens, David C. ^{[19
]}

Rowe, Dominic B. ^{[20
]}

Sachdev, Perminder ^{[21
,22
]}

Shah, Sonia ^{[1
]}

Song, Sharon ^{[4
,5
]}

Tan, Li-Jun ^{[7
,8
]}

Tang, Lu ^{[3
]}

van den Berg, Leonard H. ^{[23
]}

van Rheenen, Wouter ^{[23
]}

Veldink, Jan H. ^{[23
]}

Wallace, Robyn H. ^{[1
]}

Wheeler, Lawrie ^{[4
,5
]}

Williams, Kelly L. ^{[11
]}

Wu, Jinyu ^{[15
]}

Wu, Xin ^{[15
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[2] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia

[3] Peking Univ, Dept Neurol, Hosp 3, 49 North Garden Rd, Beijing 100191, Peoples R China

[4] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia

[5] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Translat Res Inst, Brisbane, Qld 4102, Australia

[6] Kings Coll London, Maurice Wohl Clin Neurosci Inst, Dept Basic & Clin Neurosci, London WC2 R2LS, England

[7] Hunan Normal Univ, Coll Life Sci, Lab Mol & Stat Genet, Changsha 410081, Hunan, Peoples R China

[8] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Hunan, Peoples R China

[9] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Biostat & Data Sci, Ctr Bioinformat & Genom, 1440 Canal St,Suite 2001, New Orleans, LA 70112 USA

[10] Royal Brisbane & Womens Hosp, Dept Neurol, Brisbane, Qld 4029, Australia

[11] Macquarie Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Sydney, NSW 2109, Australia

[12] Univ Shanghai Sci & Technol, Ctr Syst Biomed Sci, 334 Jungong Rd, Shanghai 200093, Peoples R China

[13] Royal Brisbane & Womens Hosp, Kenneth G Jamieson Dept Neurosurg, Herston, Qld 4029, Australia

[14] Wenzhou Med Univ, Eye Hosp, Div Ophthalm Genet, Lab Stem Cell & Retinal Regenerat, Wenzhou 325027, Peoples R China

[15] Wenzhou Med Univ, Inst Genom Med, Wenzhou 325027, Peoples R China

[16] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai 200003, Peoples R China

[17] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia

[18] Univ Sydney, Discipline Pathol Brain & Mind Ctr, Stacey MND Lab, Sydney, NSW 2006, Australia

[19] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia

[20] Macquarie Univ, Fac Med & Hlth Sci, Dept Med, Multidisciplinary Motor Neurone Dis Clin, Sydney, NSW 2109, Australia

[21] Univ New South Wales, Fac Med, Sch Psychiat, Ctr Healthy Brain Ageing, Sydney, NSW 2052, Australia

[22] Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW 2031, Australia

[23] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, NL-3584 CG Utrecht, Netherlands

[24] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing 100191, Peoples R China

[25] Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100191, Peoples R China

[26] Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing 100191, Peoples R China

[27] Univ Queensland, Royal Brisbane & Womens Hosp, UQ Ctr Clin Res, Brisbane, Qld 4029, Australia

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 澳大利亚研究理事会; 中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-CORRELATION; SUSCEPTIBILITY; PROPORTION; VARIANTS; ONSET; GWAS; ALS;

D O I：

10.1038/s41467-017-00471-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 x 10(-8)), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 x 10(-3)). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.

引用

页数：7

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