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van Es, M.A.* ; Veldink, J.H.* ; Saris, C.G.* ; Blauw, H.M.* ; van Vught, P.W.* ; Birve, A.* ; Lemmens, R.* ; Schelhaas, H.J.* ; Groen, E.J.* ; Huisman, M.H.* ; van der Kooi, A.J.* ; de Visser, M.* ; Dahlberg, C.* ; Estrada, K.* ; Rivadeneira, F.* ; Hofman, A.* ; Zwarts, M.J.* ; van Doormaal, P.T.* ; Rujescu, D.* ; Strengman, E.* ; Giegling, I.* ; Muglia, P.* ; Tomik, B.* ; Slowik, A.* ; Uitterlinden, A.G.* ; Hendrich, C.* ; Waibel, S.* ; Meyer, T.* ; Ludolph, A.C.* ; Glass, J.D.* ; Purcell, S.* ; Cichon, S.* ; Nöthen, M.M.* ; Wichmann, H.-E. ; Schreiber, S.* ; Vermeulen, S.H.* ; Kiemeney, L.A.* ; Wokke, J.H.* ; Cronin, S.* ; McLaughlin, R.L.* ; Hardiman, O.* ; Fumoto, K.* ; Pasterkamp, R.J.* ; Meininger, V.* ; Melki, J.* ; Leigh, P.N.* ; Shaw, C.E.* ; Landers, J.E.* ; Al-Chalabi, A.* ; Brown, R.H.Jr.* ; Robberecht, W.* ; Andersen, P.M.* ; Ophoff, R.A.* ; van den Berg, L.H.*

Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis.

Nat. Genet. 41, 1083-1087 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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Publication type Article: Journal article
Document type Scientific Article
Keywords frontotemporal dementia; confers susceptibility; chromosome 9P; population; disease; variants; release; linkage; hapmap; design
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 41, Issue: 10, Pages: 1083-1087 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)