No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

A. Goris; J. van Setten; F. Diekstra; S. Ripke; N.A. Patsopoulos; S.J. Sawcer; M. van Es; P.M. Andersen; J. Melki; V. Meininger; O. Hardiman; J.E. Landers; R.H. Brown; A. Shatunov; N. Leigh; A. Al-Chalabi; C.E. Shaw; B.J. Traynor; A. Chio; G. Restagno; G. Mora; R.A. Ophoff; J.R. Oksenberg; P. Van Damme; A. Compston; W. Robberecht; B. Dubois; L.H. van den Berg; P.L. De Jager; J.H. Veldink; P.I.W. de Bakker; A.G. Kermode

doi:10.1093/hmg/ddt574

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No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

Journal article

Peer reviewed

No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

A. Goris, J. van Setten, F. Diekstra, S. Ripke, N.A. Patsopoulos, S.J. Sawcer, M. van Es, P.M. Andersen, J. Melki, V. Meininger, …

Human Molecular Genetics, Vol.23(7), pp.1916-1922

2014

DOI: https://doi.org/10.1093/hmg/ddt574

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Abstract

Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.

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Title: No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis
Authors/Creators: A. Goris (Author/Creator) - KU Leuven
J. van Setten (Author/Creator) - University Medical Center Utrecht
F. Diekstra (Author/Creator) - University Medical Center Utrecht
S. Ripke (Author/Creator) - Massachusetts General Hospital
N.A. Patsopoulos (Author/Creator) - Brigham and Women's Hospital
S.J. Sawcer (Author/Creator) - Addenbrooke's Hospital
M. van Es (Author/Creator) - University Medical Center Utrecht
P.M. Andersen (Author/Creator) - Université Paris Cité
J. Melki (Author/Creator) - Sorbonne Université
V. Meininger (Author/Creator) - Beaumont Hospital
O. Hardiman (Author/Creator) - University of Massachusetts Chan Medical School
J.E. Landers (Author/Creator) - University of Massachusetts Chan Medical School
R.H. Brown (Author/Creator) - King's College London
A. Shatunov (Author/Creator) - King's College London
N. Leigh (Author/Creator) - King's College London
A. Al-Chalabi (Author/Creator) - King's College London
C.E. Shaw (Author/Creator) - National Institute on Aging
B.J. Traynor (Author/Creator) - Azienda Ospedaliera Citta' della Salute e della Scienza di Torino
A. Chio (Author/Creator) - Azienda Ospedaliera Citta' della Salute e della Scienza di Torino
G. Restagno (Author/Creator) - Fondazione Salvatore Maugeri
G. Mora (Author/Creator) - University of California, Los Angeles
R.A. Ophoff (Author/Creator) - University of California, San Francisco
J.R. Oksenberg (Author/Creator) - KU Leuven
P. Van Damme (Author/Creator) - Addenbrooke's Hospital
A. Compston (Author/Creator) - KU Leuven
W. Robberecht (Author/Creator) - KU Leuven
B. Dubois (Author/Creator) - University Medical Center Utrecht
L.H. van den Berg (Author/Creator) - Broad Institute
P.L. De Jager (Author/Creator) - University Medical Center Utrecht
J.H. Veldink (Author/Creator) - University Medical Center Utrecht
P.I.W. de Bakker (Author/Creator) - University Medical Center Utrecht
A.G. Kermode (Author/Creator)
Publication Details: Human Molecular Genetics, Vol.23(7), pp.1916-1922
Publisher: Oxford University Press
Identifiers: 991005544349907891
Copyright: © The Author 2013.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.765 ALS Mechanisms
Web Of Science research areas: Biochemistry & Molecular Biology; Genetics & Heredity
ESI research areas: Molecular Biology & Genetics