A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

Isabella Fogh; Antonia Ratti; Cinzia Gellera; Kuang Lin; Cinzia Tiloca; Valentina Moskvina; Lucia Corrado; Gianni Sorarù; Cristina Cereda; Stefania Corti; Davide Gentilini; Daniela Calini; Barbara Castellotti; Letizia Mazzini; Giorgia Querin; Stella Gagliardi; Roberto Del bo; Francesca L. Conforti; Gabriele Siciliano; Maurizio Inghilleri; Francesco Saccà; Paolo Bongioanni; Silvana Penco; Massimo Corbo; Sandro Sorbi; Massimiliano Filosto; Alessandra Ferlini; Anna M. Di blasio; Stefano Signorini; Aleksey Shatunov; Ashley Jones; Pamela J. Shaw; Karen E. Morrison; Anne E. Farmer; Philip Van damme; Wim Robberecht; Adriano Chiò; Bryan J. Traynor; Michael Sendtner; Judith Melki; Vincent Meininger; Orla Hardiman; Peter M. Andersen; Nigel P. Leigh; Jonathan D. Glass; Daniel Overste; Frank P. Diekstra; Jan H. Veldink; Michael A. Van es; Christopher E. Shaw; Michael E. Weale; Cathryn M. Lewis; Julie Williams; Robert H. Brown; John E. Landers; Nicola Ticozzi; Mauro Ceroni; Elena Pegoraro; Giacomo P. Comi; Sandra D'alfonso; Leonard H. Van den berg; Franco Taroni; Ammar Al-chalabi; John Powell; Vincenzo Silani

doi:10.1093/hmg/ddt587

A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

Isabella Fogh, Antonia Ratti, Cinzia Gellera, Kuang Lin, Cinzia Tiloca, Valentina Moskvina, Lucia Corrado, Gianni Sorarù, Cristina Cereda, Stefania Corti, Davide Gentilini, Daniela Calini, Barbara Castellotti, Letizia Mazzini, Giorgia Querin, Stella Gagliardi, Roberto Del bo, Francesca L. Conforti, Gabriele Siciliano, Maurizio InghilleriFrancesco Saccà, Paolo Bongioanni, Silvana Penco, Massimo Corbo, Sandro Sorbi, Massimiliano Filosto, Alessandra Ferlini, Anna M. Di blasio, Stefano Signorini, Aleksey Shatunov, Ashley Jones, Pamela J. Shaw, Karen E. Morrison, Anne E. Farmer, Philip Van damme, Wim Robberecht, Adriano Chiò, Bryan J. Traynor, Michael Sendtner, Judith Melki, Vincent Meininger, Orla Hardiman, Peter M. Andersen, Nigel P. Leigh, Jonathan D. Glass, Daniel Overste, Frank P. Diekstra, Jan H. Veldink, Michael A. Van es, Christopher E. Shaw, Michael E. Weale, Cathryn M. Lewis, Julie Williams, Robert H. Brown, John E. Landers, Nicola Ticozzi, Mauro Ceroni, Elena Pegoraro, Giacomo P. Comi, Sandra D'alfonso, Leonard H. Van den berg, Franco Taroni, Ammar Al-chalabi, John Powell, Vincenzo Silani

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (~90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10^-8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10^-9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10^-9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ~12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.

Lingua originale	Inglese
pagine (da-a)	2220-2231
Numero di pagine	12
Rivista	Human Molecular Genetics
Volume	23
Numero di pubblicazione	8
DOI	https://doi.org/10.1093/hmg/ddt587
Stato di pubblicazione	Pubblicato - apr 2014

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10.1093/hmg/ddt587

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Fogh, I., Ratti, A., Gellera, C., Lin, K., Tiloca, C., Moskvina, V., Corrado, L., Sorarù, G., Cereda, C., Corti, S., Gentilini, D., Calini, D., Castellotti, B., Mazzini, L., Querin, G., Gagliardi, S., Del bo, R., Conforti, F. L., Siciliano, G., ... Silani, V. (2014). A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis. Human Molecular Genetics, 23(8), 2220-2231. https://doi.org/10.1093/hmg/ddt587

@article{b07e31eeed514623b28443272e329195,

title = "A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis",

abstract = "Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (~90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10-8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10-9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10-9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ~12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.",

author = "Isabella Fogh and Antonia Ratti and Cinzia Gellera and Kuang Lin and Cinzia Tiloca and Valentina Moskvina and Lucia Corrado and Gianni Sorar{\`u} and Cristina Cereda and Stefania Corti and Davide Gentilini and Daniela Calini and Barbara Castellotti and Letizia Mazzini and Giorgia Querin and Stella Gagliardi and {Del bo}, Roberto and Conforti, {Francesca L.} and Gabriele Siciliano and Maurizio Inghilleri and Francesco Sacc{\`a} and Paolo Bongioanni and Silvana Penco and Massimo Corbo and Sandro Sorbi and Massimiliano Filosto and Alessandra Ferlini and {Di blasio}, {Anna M.} and Stefano Signorini and Aleksey Shatunov and Ashley Jones and Shaw, {Pamela J.} and Morrison, {Karen E.} and Farmer, {Anne E.} and {Van damme}, Philip and Wim Robberecht and Adriano Chi{\`o} and Traynor, {Bryan J.} and Michael Sendtner and Judith Melki and Vincent Meininger and Orla Hardiman and Andersen, {Peter M.} and Leigh, {Nigel P.} and Glass, {Jonathan D.} and Daniel Overste and Diekstra, {Frank P.} and Veldink, {Jan H.} and {Van es}, {Michael A.} and Shaw, {Christopher E.} and Weale, {Michael E.} and Lewis, {Cathryn M.} and Julie Williams and Brown, {Robert H.} and Landers, {John E.} and Nicola Ticozzi and Mauro Ceroni and Elena Pegoraro and Comi, {Giacomo P.} and Sandra D'alfonso and {Van den berg}, {Leonard H.} and Franco Taroni and Ammar Al-chalabi and John Powell and Vincenzo Silani",

note = "Funding Information: The SLAGEN Consortium was supported by funds from the Ministero della Salute Italiano (GWA-SLA, Ricerca Finalizzata 2007 grant number 31) and Fondazione Istituto Auxologico Italiano; I.F., C.G., B.C., J.F.P. and V.S. were supported by the Istituto Superiore di Sanit{\`a} (grant number 526D/34, 2006); I.F. received salary support from {\textquoteleft}Amici del Centro Dino Ferrari{\textquoteright}; V.S. acknowledges support from the {\textquoteleft}Amici del Centro Dino Ferrari{\textquoteright}. A.R., C.G., B.C., N.T. and V.S. were supported by the Ministero della Salute Italiano (ALS-FTD, RF-2009-1473856); G.Si. was supported by Monte dei Paschi di Siena Foundation (grant 39167) and the Ministero della Salute Italiano (grant number RF-INP-2007-627227); A.C. was supported in part by Federazione Italiana Giuoco Calcio and Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus, Ministero della Salute Italiano (grant number RF-PIE-2007-635695); AF was supported by Progetto Regione Emilia Romagna-Universit{\`a} {\textquoteleft}RARER{\textquoteright}. The Italian replica control samples were obtained from the {\textquoteleft}Parkinson Institute Biobank{\textquoteright} (http://www.parkinsonbiobank.com) of the Telethon Genetic Biobank Network (http://www.biobanknetwork.org) supported by TELETHON Italy (grant number GTB07001) and by {\textquoteleft}Fonda-zione Grigioni per il Morbo di Parkinson{\textquoteright}. ALSAGEN Consortium is supported by funds from the National Institutes for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, King{\textquoteright}s College London, the University of Leuven (grant number GOA/11/014), the Interuniversity Attraction Poles (IUAP) program P7/16 of the Belgian Federal Science Policy Office and the 7th Framework Programme of the European Union (ADAMS project, grant numbers HEALTH-F4-2009-242257 and FP7/2007-2013, grant agreements 259867 and 278611). P.V.D. holds a clinical investigatorship from FWO-Vlaanderen; W.R. is supported through the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders. The UK National DNA Bank for Motor Neuron Disease Research was funded by the Motor Neurone Disease Association (grant 3/3), the Wellcome Trust (grant number 070122/A/02/Z) and the National Institute for Health Research Dementias and Neurodegenerative Diseases Research Network. A.A.-C. and J.F.P. receive salary support from the National Institute for Health Research Dementia Biomedical Research Unit at South London and Maudsley National Health Service Foundation Trust and King{\textquoteright}s College London. The RADIANT depression and bipolar case control studies (DeCC, BACC) were genotyped under Medical Research Council (grant number G0701420). A.A.-C. thanks the Motor Neurone Disease Association of Great Britain and Northern Ireland, the ALS Association, the ALS Therapy Alliance and the Medical Research Council (grant number G0600974) for support. R.H.B. acknowledges support from the National Institute of Neurological Disorders and Stroke (grant number 5RO1-NS050557-05) and the National Institute of Neurological Disorders and Stroke American Recovery and Reinvestment Act Award (grant number RC2-NS070-342), the Angel Fund, the ALS Association, P2ALS, Project ALS, the Pierre L. de Bourg-knecht ALS Research Foundation and the ALS Therapy Alliance. J.E.L. acknowledges grant support from National Institute of Health/ National Institute of Neurological Disorders and Stroke (grant number 1R01NS073873). The Dutch, Belgian and Swedish GWAS data generation was supported by the Prinses Beatrix Fonds, VSB fonds, H. Kersten and M. Kersten (Kersten Foundation), The Netherlands ALS Foundation, and J.R. van Dijk and the Adessium Foundation. Funding Information: Genetic and statistical analysis was performed using a Linux cluster supported by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry King{\textquoteright}s College London. G.So. acknowledges EuroBiobank for ALS DNA samples; K.M. acknowledges Motor Neurone Disease Association UK, Queen Elizabeth Hospital Birmingham Charity. M.S. acknowledges support through EU via the Euro-MOTOR consortium and German BMBF Motoneuron disease network.",

year = "2014",

month = apr,

doi = "10.1093/hmg/ddt587",

language = "English",

volume = "23",

pages = "2220--2231",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "8",

}

Fogh, I, Ratti, A, Gellera, C, Lin, K, Tiloca, C, Moskvina, V, Corrado, L, Sorarù, G, Cereda, C, Corti, S, Gentilini, D, Calini, D, Castellotti, B, Mazzini, L, Querin, G, Gagliardi, S, Del bo, R, Conforti, FL, Siciliano, G, Inghilleri, M, Saccà, F, Bongioanni, P, Penco, S, Corbo, M, Sorbi, S, Filosto, M, Ferlini, A, Di blasio, AM, Signorini, S, Shatunov, A, Jones, A, Shaw, PJ, Morrison, KE, Farmer, AE, Van damme, P, Robberecht, W, Chiò, A, Traynor, BJ, Sendtner, M, Melki, J, Meininger, V, Hardiman, O, Andersen, PM, Leigh, NP, Glass, JD, Overste, D, Diekstra, FP, Veldink, JH, Van es, MA, Shaw, CE, Weale, ME, Lewis, CM, Williams, J, Brown, RH, Landers, JE, Ticozzi, N, Ceroni, M, Pegoraro, E, Comi, GP, D'alfonso, S, Van den berg, LH, Taroni, F, Al-chalabi, A, Powell, J & Silani, V 2014, 'A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis', Human Molecular Genetics, vol. 23, n. 8, pagg. 2220-2231. https://doi.org/10.1093/hmg/ddt587

TY - JOUR

T1 - A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

AU - Fogh, Isabella

AU - Ratti, Antonia

AU - Gellera, Cinzia

AU - Lin, Kuang

AU - Tiloca, Cinzia

AU - Moskvina, Valentina

AU - Corrado, Lucia

AU - Sorarù, Gianni

AU - Cereda, Cristina

AU - Corti, Stefania

AU - Gentilini, Davide

AU - Calini, Daniela

AU - Castellotti, Barbara

AU - Mazzini, Letizia

AU - Querin, Giorgia

AU - Gagliardi, Stella

AU - Del bo, Roberto

AU - Conforti, Francesca L.

AU - Siciliano, Gabriele

AU - Inghilleri, Maurizio

AU - Saccà, Francesco

AU - Bongioanni, Paolo

AU - Penco, Silvana

AU - Corbo, Massimo

AU - Sorbi, Sandro

AU - Filosto, Massimiliano

AU - Ferlini, Alessandra

AU - Di blasio, Anna M.

AU - Signorini, Stefano

AU - Shatunov, Aleksey

AU - Jones, Ashley

AU - Shaw, Pamela J.

AU - Morrison, Karen E.

AU - Farmer, Anne E.

AU - Van damme, Philip

AU - Robberecht, Wim

AU - Chiò, Adriano

AU - Traynor, Bryan J.

AU - Sendtner, Michael

AU - Melki, Judith

AU - Meininger, Vincent

AU - Hardiman, Orla

AU - Andersen, Peter M.

AU - Leigh, Nigel P.

AU - Glass, Jonathan D.

AU - Overste, Daniel

AU - Diekstra, Frank P.

AU - Veldink, Jan H.

AU - Van es, Michael A.

AU - Shaw, Christopher E.

AU - Weale, Michael E.

AU - Lewis, Cathryn M.

AU - Williams, Julie

AU - Brown, Robert H.

AU - Landers, John E.

AU - Ticozzi, Nicola

AU - Ceroni, Mauro

AU - Pegoraro, Elena

AU - Comi, Giacomo P.

AU - D'alfonso, Sandra

AU - Van den berg, Leonard H.

AU - Taroni, Franco

AU - Al-chalabi, Ammar

AU - Powell, John

AU - Silani, Vincenzo

N1 - Funding Information: The SLAGEN Consortium was supported by funds from the Ministero della Salute Italiano (GWA-SLA, Ricerca Finalizzata 2007 grant number 31) and Fondazione Istituto Auxologico Italiano; I.F., C.G., B.C., J.F.P. and V.S. were supported by the Istituto Superiore di Sanità (grant number 526D/34, 2006); I.F. received salary support from ‘Amici del Centro Dino Ferrari’; V.S. acknowledges support from the ‘Amici del Centro Dino Ferrari’. A.R., C.G., B.C., N.T. and V.S. were supported by the Ministero della Salute Italiano (ALS-FTD, RF-2009-1473856); G.Si. was supported by Monte dei Paschi di Siena Foundation (grant 39167) and the Ministero della Salute Italiano (grant number RF-INP-2007-627227); A.C. was supported in part by Federazione Italiana Giuoco Calcio and Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus, Ministero della Salute Italiano (grant number RF-PIE-2007-635695); AF was supported by Progetto Regione Emilia Romagna-Università ‘RARER’. The Italian replica control samples were obtained from the ‘Parkinson Institute Biobank’ (http://www.parkinsonbiobank.com) of the Telethon Genetic Biobank Network (http://www.biobanknetwork.org) supported by TELETHON Italy (grant number GTB07001) and by ‘Fonda-zione Grigioni per il Morbo di Parkinson’. ALSAGEN Consortium is supported by funds from the National Institutes for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, King’s College London, the University of Leuven (grant number GOA/11/014), the Interuniversity Attraction Poles (IUAP) program P7/16 of the Belgian Federal Science Policy Office and the 7th Framework Programme of the European Union (ADAMS project, grant numbers HEALTH-F4-2009-242257 and FP7/2007-2013, grant agreements 259867 and 278611). P.V.D. holds a clinical investigatorship from FWO-Vlaanderen; W.R. is supported through the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders. The UK National DNA Bank for Motor Neuron Disease Research was funded by the Motor Neurone Disease Association (grant 3/3), the Wellcome Trust (grant number 070122/A/02/Z) and the National Institute for Health Research Dementias and Neurodegenerative Diseases Research Network. A.A.-C. and J.F.P. receive salary support from the National Institute for Health Research Dementia Biomedical Research Unit at South London and Maudsley National Health Service Foundation Trust and King’s College London. The RADIANT depression and bipolar case control studies (DeCC, BACC) were genotyped under Medical Research Council (grant number G0701420). A.A.-C. thanks the Motor Neurone Disease Association of Great Britain and Northern Ireland, the ALS Association, the ALS Therapy Alliance and the Medical Research Council (grant number G0600974) for support. R.H.B. acknowledges support from the National Institute of Neurological Disorders and Stroke (grant number 5RO1-NS050557-05) and the National Institute of Neurological Disorders and Stroke American Recovery and Reinvestment Act Award (grant number RC2-NS070-342), the Angel Fund, the ALS Association, P2ALS, Project ALS, the Pierre L. de Bourg-knecht ALS Research Foundation and the ALS Therapy Alliance. J.E.L. acknowledges grant support from National Institute of Health/ National Institute of Neurological Disorders and Stroke (grant number 1R01NS073873). The Dutch, Belgian and Swedish GWAS data generation was supported by the Prinses Beatrix Fonds, VSB fonds, H. Kersten and M. Kersten (Kersten Foundation), The Netherlands ALS Foundation, and J.R. van Dijk and the Adessium Foundation. Funding Information: Genetic and statistical analysis was performed using a Linux cluster supported by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry King’s College London. G.So. acknowledges EuroBiobank for ALS DNA samples; K.M. acknowledges Motor Neurone Disease Association UK, Queen Elizabeth Hospital Birmingham Charity. M.S. acknowledges support through EU via the Euro-MOTOR consortium and German BMBF Motoneuron disease network.

PY - 2014/4

Y1 - 2014/4

N2 - Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (~90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10-8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10-9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10-9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ~12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.

AB - Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (~90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10-8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10-9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10-9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ~12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.

UR - http://www.scopus.com/inward/record.url?scp=84897859556&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddt587

DO - 10.1093/hmg/ddt587

M3 - Article

SN - 0964-6906

VL - 23

SP - 2220

EP - 2231

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 8

ER -

A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

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