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

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 ca...

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Hauptverfasser: Van Rheenen, Wouter (VerfasserIn) , Rietschel, Marcella (VerfasserIn) , Nöthen, Markus Maria (VerfasserIn) , Weishaupt, Jochen H. (VerfasserIn)
Dokumenttyp: Article (Journal) Editorial
Sprache:Englisch
Veröffentlicht: 25 July 2016
In: Nature genetics
Year: 2016, Jahrgang: 48, Heft: 9, Pages: 1043-1048
ISSN:1546-1718
DOI:10.1038/ng.3622
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1038/ng.3622
Verlag, Volltext: http://www.nature.com/articles/ng.3622
Volltext
Verfasserangaben:Wouter van Rheenen, Marcella Rietschel, Marcus M Nöthen, Jochen H Weishaupt [und 175 weitere]
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Zusammenfassung: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.
Beschreibung:Gesehen am 21.01.2019
Beschreibung:Online Resource
ISSN:1546-1718
DOI:10.1038/ng.3622

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