Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
International audience ; 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... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2016 |
Verlag/Hrsg.: |
HAL CCSD
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Schlagwörter: | MESH: Amyotrophic Lateral Sclerosis / MESH: Case-Control Studies / MESH: Genetic Predisposition to Disease / MESH: Genome-Wide Association Study / MESH: Humans / MESH: Munc18 Proteins / MESH: Mutation / MESH: Myelin Proteins / MESH: Netherlands / MESH: Proteins / MESH: Cohort Studies / MESH: Cytoskeletal Proteins / [SDV]Life Sciences [q-bio] |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-27212582 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://hal.science/hal-03939751 |
International audience ; 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.