2009-10-01
Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
Publication
Publication
Nature Genetics , Volume 41 - Issue 10 p. 1083- 1087
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 × 104 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 × 109. This SNP showed robust replication in the second cohort (P = 1.86 × 106), and a combined analysis over the two stages yielded P = 2.53 × 1014. 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 × 109, and rs3849942, with P = 1.01 × 108) 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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| doi.org/10.1038/ng.442, hdl.handle.net/1765/24582 | |
| Nature Genetics | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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van Es, M., Veldink, J., Saris, C., Blauw, H., van Vught, P., Birve, A., Lemmens, R., Schelhaas, H., Groen, E., Huisman, M., Kooj, A., de Visser, M., Dahlberg, C., Estrada Gil, K., Rivadeneira Ramirez, F., Hofman, A., Zwarts, M. J., van Doormaal, P., Rujescu, D., … van den Berg, L. (2009). Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nature Genetics, 41(10), 1083–1087.https://doi.org/10.1038/ng.442 |
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