Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

Leigh, P. Nigel and et al, (2016) Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nature Genetics, 48 (9). pp. 1043-1048. ISSN 1061-4036

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Abstract

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1–10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.

Item Type: Article
Keywords: Genome-wide association studies Motor neuron disease
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Patricia Butler
Date Deposited: 30 Jan 2017 10:06
Last Modified: 25 Jul 2017 15:19
URI: http://sro.sussex.ac.uk/id/eprint/66488
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