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Title: Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
Authors: van Es, Michael A ×
Veldink, Jan H
Saris, Christiaan G J
Blauw, Hylke M
van Vught, Paul W J
Birve, Anna
Lemmens, Robin
Schelhaas, Helenius J
Groen, Ewout J N
Huisman, Mark H B
van der Kooi, Anneke J
de Visser, Marianne
Dahlberg, Caroline
Estrada, Karol
Rivadeneira, Fernando
Hofman, Albert
Zwarts, Machiel J
van Doormaal, Perry T C
Rujescu, Dan
Strengman, Eric
Giegling, Ina
Muglia, Pierandrea
Tomik, Barbara
Slowik, Agnieszka
Uitterlinden, Andre G
Hendrich, Corinna
Waibel, Stefan
Meyer, Thomas
Ludolph, Albert C
Glass, Jonathan D
Purcell, Shaun
Cichon, Sven
Nöthen, Markus M
Wichmann, H-Erich
Schreiber, Stefan
Vermeulen, Sita H H M
Kiemeney, Lambertus A
Wokke, John H J
Cronin, Simon
McLaughlin, Russell L
Hardiman, Orla
Fumoto, Katsumi
Pasterkamp, R Jeroen
Meininger, Vincent
Melki, Judith
Leigh, P Nigel
Shaw, Christopher E
Landers, John E
Al-Chalabi, Ammar
Brown, Robert H
Robberecht, Wim
Andersen, Peter M
Ophoff, Roel A
van den Berg, Leonard H #
Issue Date: Oct-2009
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:41 issue:10 pages:1083-U53
Abstract: 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.
ISSN: 1061-4036
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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