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Title: A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis
Authors: Fogh, Isabella ×
Ratti, Antonia
Gellera, Cinzia
Lin, Kuang
Tiloca, Cinzia
Moskvina, Valentina
Corrado, Lucia
Sorarù, Gianni
Cereda, Cristina
Corti, Stefania
Gentilini, Davide
Calini, Daniela
Castellotti, Barbara
Mazzini, Letizia
Querin, Giorgia
Gagliardi, Stella
Del Bo, Roberto
Conforti, Francesca L
Siciliano, Gabriele
Inghilleri, Maurizio
Saccà, Francesco
Bongioanni, Paolo
Penco, Silvana
Corbo, Massimo
Sorbi, Sandro
Filosto, Massimiliano
Ferlini, Alessandra
Di Blasio, Anna M
Signorini, Stefano
Shatunov, Aleksey
Jones, Ashley
Shaw, Pamela J
Morrison, Karen E
Farmer, Anne E
Van Damme, Philip
Robberecht, Wim
Chiò, Adriano
Traynor, Bryan J
Sendtner, Michael
Melki, Judith
Meininger, Vincent
Hardiman, Orla
Andersen, Peter M
Leigh, Nigel P
Glass, Jonathan D
Overste, Daniel
Diekstra, Frank P
Veldink, Jan H
van Es, Michael A
Shaw, Christopher E
Weale, Michael E
Lewis, Cathryn M
Williams, Julie
Brown, Robert H
Landers, John E
Ticozzi, Nicola
Ceroni, Mauro
Pegoraro, Elena
Comi, Giacomo P
D'Alfonso, Sandra
van den Berg, Leonard H
Taroni, Franco
Al-Chalabi, Ammar
Powell, John
Silani, Vincenzo
the SLAGEN Consortium Collaborators #
Issue Date: Apr-2014
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:23 issue:8 pages:2220-31
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 3,959 newly genotyped Italian individuals (1,982 cases, 1,977 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 analyzed a total of 13,225 individuals, 6,100 cases and 7,125 controls for almost 7 million single nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 P=1.11 x 10(-8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P=8.62 x 10(-9); OR 0.833) of 4,656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P=7.69 x 10(-9); OR 1.16). Finally, we have 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.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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