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; 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 S. 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

doi:10.1038/s41467-017-00471-1

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 HanJessica 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 S. 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 journal › Article › Academic › peer-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.

Original language	English
Article number	611
Pages (from-to)	1-7
Journal	Nature Communications [E]
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00471-1
Publication status	Published - 20 Sept 2017

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Benyamin, B., He, J., Zhao, Q., Gratten, J., Garton, F., Leo, P. J., Liu, Z., Mangelsdorf, M., Al-Chalabi, A., Anderson, L., Butler, T. J., Chen, L., Chen, X.-D., Cremin, K., Deng, H.-W., Devine, M., Edson, J., Fifita, J. A., Furlong, S., ... Fan, D. (2017). Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis. Nature Communications [E], 8(1), 1-7. Article 611. https://doi.org/10.1038/s41467-017-00471-1

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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.",

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year = "2017",

month = sep,

day = "20",

doi = "10.1038/s41467-017-00471-1",

language = "English",

volume = "8",

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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, X-D, Cremin, K, Deng, H-W, Devine, M, Edson, J, Fifita, JA, Furlong, S, Han, Y-Y, Harris, J, Henders, AK, Jeffree, RL, Jin, Z-B, 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, PS, Shah, S, Song, S, Tan, L-J, 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, Z-H, 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 [E], vol. 8, no. 1, 611, pp. 1-7. https://doi.org/10.1038/s41467-017-00471-1

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 S.

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

PY - 2017/9/20

Y1 - 2017/9/20

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.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85029654904&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00471-1

DO - 10.1038/s41467-017-00471-1

M3 - Article

C2 - 28931804

SN - 2041-1723

VL - 8

SP - 1

EP - 7

JO - Nature Communications [E]

JF - Nature Communications [E]

IS - 1

M1 - 611

ER -

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

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