Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.
Nat. Genet. 48, 1043-1048 (2016)
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Frontotemporal Dementia; Hexanucleotide Repeat; Als; Susceptibility; Population; Efficient; Pathways; Pitfalls; Sequence; Complex
ISSN (print) / ISBN 1061-4036
Zeitschrift Nature Genetics
Quellenangaben Band: 48, Heft: 9, Seiten: 1043-1048
Verlag Nature America
Verlagsort New York, NY
Institut(e) Institute of Human Genetics (IHG)