van Rheenen, W;
Shatunov, A;
Dekker, AM;
McLaughlin, RL;
Diekstra, FP;
Pulit, SL;
van der Spek, RAA;
... Veldink, JH; + view all
(2016)
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.
Nature Genetics
, 48
(9)
pp. 1043-1048.
10.1038/ng.3622.
Preview |
Text
Orrell_MinE_GWAS_manuscript_NG.pdf - Accepted Version Download (263kB) | Preview |
Abstract
To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genomesequenced 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.
Archive Staff Only
 |
View Item |
