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

Beben Benyamin, Ji He, Qiongyi Zhao, Jacob Gratten, Fleur Garton, Paul J. Leo, Zhijun Liu, Marie Mangelsdorf, Ammar Al-Chalabi, Lisa Anderson, Timothy J. Butler, Lu Chen, Xiang Ding Chen, Katie Cremin, Hong Weng Deng, Matthew Devine, Janette Edson, Jennifer A. Fifita, Sarah Furlong, Ying Ying Han & 44 others Jessica Harris, Anjali K. Henders, Rosalind L. Jeffree, Zi Bing Jin, Zhongshan Li, Ting Li, Mengmeng Li, Yong Lin, Xiaolu Liu, Mhairi Marshall, Emily P. McCann, Bryan J. Mowry, Shyuan T. Ngo, Roger Pamphlett, Shu Ran, David C. Reutens, Dominic B. Rowe, Perminder Sachdev, Sonia Shah, Sharon Song, Li Jun Tan, Lu Tang, Leonard H. Van Den Berg, Wouter Van Rheenen, Jan H. Veldink, Robyn H. Wallace, Lawrie Wheeler, Kelly L. Williams, Jinyu Wu, Xin Wu, Jian Yang, Weihua Yue, Zong Hong Zhang, Dai Zhang, Peter G. Noakes, Ian P. Blair, Robert D. Henderson, Pamela A. McCombe, Peter M. Visscher, Huji Xu, Perry F. Bartlett, Matthew A. Brown, Naomi R. Wray, Dongsheng Fan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 × 10-8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 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.

LanguageEnglish
Article number611
Pages1-7
Number of pages7
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 1 Dec 2017

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Amyotrophic Lateral Sclerosis
loci
Genetic Crosses
Meta-Analysis
Genes
genes
Mendelian Randomization Analysis
Chromosome Mapping
Genome-Wide Association Study
Linkage Disequilibrium
Population Genetics
epidemiology
Neurodegenerative diseases
etiology
Ethnic Groups
Gene Frequency
Neurodegenerative Diseases
Epidemiology
genome
linkages

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

Benyamin, Beben ; He, Ji ; Zhao, Qiongyi ; Gratten, Jacob ; Garton, Fleur ; Leo, Paul J. ; Liu, Zhijun ; Mangelsdorf, Marie ; Al-Chalabi, Ammar ; Anderson, Lisa ; Butler, Timothy J. ; Chen, Lu ; Chen, Xiang Ding ; Cremin, Katie ; Deng, Hong Weng ; Devine, Matthew ; Edson, Janette ; Fifita, Jennifer A. ; Furlong, Sarah ; Han, Ying Ying ; Harris, Jessica ; Henders, Anjali K. ; Jeffree, Rosalind L. ; Jin, Zi Bing ; Li, Zhongshan ; Li, Ting ; Li, Mengmeng ; Lin, Yong ; Liu, Xiaolu ; Marshall, Mhairi ; McCann, Emily P. ; Mowry, Bryan J. ; Ngo, Shyuan T. ; Pamphlett, Roger ; Ran, Shu ; Reutens, David C. ; Rowe, Dominic B. ; Sachdev, Perminder ; Shah, Sonia ; Song, Sharon ; Tan, Li Jun ; Tang, Lu ; Van Den Berg, Leonard H. ; Van Rheenen, Wouter ; Veldink, Jan H. ; Wallace, Robyn H. ; Wheeler, Lawrie ; Williams, Kelly L. ; Wu, Jinyu ; Wu, Xin ; Yang, Jian ; Yue, Weihua ; Zhang, Zong Hong ; Zhang, Dai ; Noakes, Peter G. ; Blair, Ian P. ; Henderson, Robert D. ; McCombe, Pamela A. ; Visscher, Peter M. ; Xu, Huji ; Bartlett, Perry F. ; Brown, Matthew A. ; Wray, Naomi R. ; Fan, Dongsheng. / Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis. In: Nature Communications. 2017 ; Vol. 8. pp. 1-7.
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abstract = "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 × 10-8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 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.",
author = "Beben Benyamin and Ji He and Qiongyi Zhao and Jacob Gratten and Fleur Garton and Leo, {Paul J.} and Zhijun Liu and Marie Mangelsdorf and Ammar Al-Chalabi and Lisa Anderson and Butler, {Timothy J.} and Lu Chen and Chen, {Xiang Ding} and Katie Cremin and Deng, {Hong Weng} and Matthew Devine and Janette Edson and Fifita, {Jennifer A.} and Sarah Furlong and Han, {Ying Ying} and Jessica Harris and Henders, {Anjali K.} and Jeffree, {Rosalind L.} and Jin, {Zi Bing} and Zhongshan Li and Ting Li and Mengmeng Li and Yong Lin and Xiaolu Liu and Mhairi Marshall and McCann, {Emily P.} and Mowry, {Bryan J.} and Ngo, {Shyuan T.} and Roger Pamphlett and Shu Ran and Reutens, {David C.} and Rowe, {Dominic B.} and Perminder Sachdev and Sonia Shah and Sharon Song and Tan, {Li Jun} and Lu Tang and {Van Den Berg}, {Leonard H.} and {Van Rheenen}, Wouter and Veldink, {Jan H.} and Wallace, {Robyn H.} and Lawrie Wheeler and Williams, {Kelly L.} and Jinyu Wu and Xin Wu and Jian Yang and Weihua Yue and Zhang, {Zong Hong} and Dai Zhang and Noakes, {Peter G.} and Blair, {Ian P.} and Henderson, {Robert D.} and McCombe, {Pamela A.} and Visscher, {Peter M.} and Huji Xu and Bartlett, {Perry F.} and Brown, {Matthew A.} and Wray, {Naomi R.} and Dongsheng Fan",
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Benyamin, B, He, J, Zhao, Q, Gratten, J, Garton, F, Leo, PJ, Liu, Z, Mangelsdorf, M, Al-Chalabi, A, Anderson, L, Butler, TJ, Chen, L, Chen, XD, Cremin, K, Deng, HW, Devine, M, Edson, J, Fifita, JA, Furlong, S, Han, YY, Harris, J, Henders, AK, Jeffree, RL, Jin, ZB, Li, Z, Li, T, Li, M, Lin, Y, Liu, X, Marshall, M, McCann, EP, Mowry, BJ, Ngo, ST, Pamphlett, R, Ran, S, Reutens, DC, Rowe, DB, Sachdev, P, Shah, S, Song, S, Tan, LJ, Tang, L, Van Den Berg, LH, Van Rheenen, W, Veldink, JH, Wallace, RH, Wheeler, L, Williams, KL, Wu, J, Wu, X, Yang, J, Yue, W, Zhang, ZH, Zhang, D, Noakes, PG, Blair, IP, Henderson, RD, McCombe, PA, Visscher, PM, Xu, H, Bartlett, PF, Brown, MA, Wray, NR & Fan, D 2017, 'Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis', Nature Communications, vol. 8, 611, pp. 1-7. https://doi.org/10.1038/s41467-017-00471-1

Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis. / Benyamin, Beben; He, Ji; Zhao, Qiongyi; Gratten, Jacob; Garton, Fleur; Leo, Paul J.; Liu, Zhijun; Mangelsdorf, Marie; Al-Chalabi, Ammar; Anderson, Lisa; Butler, Timothy J.; Chen, Lu; Chen, Xiang Ding; Cremin, Katie; Deng, Hong Weng; Devine, Matthew; Edson, Janette; Fifita, Jennifer A.; Furlong, Sarah; Han, Ying Ying; Harris, Jessica; Henders, Anjali K.; Jeffree, Rosalind L.; Jin, Zi Bing; Li, Zhongshan; Li, Ting; Li, Mengmeng; Lin, Yong; Liu, Xiaolu; Marshall, Mhairi; McCann, Emily P.; Mowry, Bryan J.; Ngo, Shyuan T.; Pamphlett, Roger; Ran, Shu; Reutens, David C.; Rowe, Dominic B.; Sachdev, Perminder; Shah, Sonia; Song, Sharon; Tan, Li Jun; Tang, Lu; Van Den Berg, Leonard H.; Van Rheenen, Wouter; Veldink, Jan H.; Wallace, Robyn H.; Wheeler, Lawrie; Williams, Kelly L.; Wu, Jinyu; Wu, Xin; Yang, Jian; Yue, Weihua; Zhang, Zong Hong; Zhang, Dai; Noakes, Peter G.; Blair, Ian P.; Henderson, Robert D.; McCombe, Pamela A.; Visscher, Peter M.; Xu, Huji; Bartlett, Perry F.; Brown, Matthew A.; Wray, Naomi R.; Fan, Dongsheng.

In: Nature Communications, Vol. 8, 611, 01.12.2017, p. 1-7.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis

AU - Benyamin, Beben

AU - He, Ji

AU - Zhao, Qiongyi

AU - Gratten, Jacob

AU - Garton, Fleur

AU - Leo, Paul J.

AU - Liu, Zhijun

AU - Mangelsdorf, Marie

AU - Al-Chalabi, Ammar

AU - Anderson, Lisa

AU - Butler, Timothy J.

AU - Chen, Lu

AU - Chen, Xiang Ding

AU - Cremin, Katie

AU - Deng, Hong Weng

AU - Devine, Matthew

AU - Edson, Janette

AU - Fifita, Jennifer A.

AU - Furlong, Sarah

AU - Han, Ying Ying

AU - Harris, Jessica

AU - Henders, Anjali K.

AU - Jeffree, Rosalind L.

AU - Jin, Zi Bing

AU - Li, Zhongshan

AU - Li, Ting

AU - Li, Mengmeng

AU - Lin, Yong

AU - Liu, Xiaolu

AU - Marshall, Mhairi

AU - McCann, Emily P.

AU - Mowry, Bryan J.

AU - Ngo, Shyuan T.

AU - Pamphlett, Roger

AU - Ran, Shu

AU - Reutens, David C.

AU - Rowe, Dominic B.

AU - Sachdev, Perminder

AU - Shah, Sonia

AU - Song, Sharon

AU - Tan, Li Jun

AU - Tang, Lu

AU - Van Den Berg, Leonard H.

AU - Van Rheenen, Wouter

AU - Veldink, Jan H.

AU - Wallace, Robyn H.

AU - Wheeler, Lawrie

AU - Williams, Kelly L.

AU - Wu, Jinyu

AU - Wu, Xin

AU - Yang, Jian

AU - Yue, Weihua

AU - Zhang, Zong Hong

AU - Zhang, Dai

AU - Noakes, Peter G.

AU - Blair, Ian P.

AU - Henderson, Robert D.

AU - McCombe, Pamela A.

AU - Visscher, Peter M.

AU - Xu, Huji

AU - Bartlett, Perry F.

AU - Brown, Matthew A.

AU - Wray, Naomi R.

AU - Fan, Dongsheng

N1 - Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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 × 10-8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 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.

AB - 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 × 10-8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 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.

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