A large genome scan for rare CNVs in amyotrophic lateral sclerosis.
Hum Mol Genet
; 19(20): 4091-9, 2010 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-20685689
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations. To examine the role of rare CNVs in ALS susceptibility, we conducted a CNV association study including over 19,000 individuals. In a genome-wide screen of 1875 cases and 8731 controls, we did not find evidence for a difference in global CNV burden between cases and controls. In our association analyses, we identified two loci that met our criteria for follow-up the DPP6 locus (OR = 3.59, P = 6.6 × 10(-3)), which has already been implicated in ALS pathogenesis, and the 15q11.2 locus, containing NIPA1 (OR = 12.46, P = 9.3 × 10(-5)), the gene causing hereditary spastic paraparesis type 6 (HSP 6). We tested these loci in a replication cohort of 2559 cases and 5887 controls. Again, results were suggestive of association, but did not meet our criteria for independent replication DPP6 locus OR = 1.92, P = 0.097, pooled results:
OR = 2.64, P = 1.4 × 10(-3); NIPA1 OR = 3.23, P = 0.041, pooledresults:
OR = 6.20, P = 2.2 × 10(-5)). Our results highlight DPP6 and NIPA1 as candidates for more in-depth studies. Unlike other complex neurological and psychiatric traits, rare CNVs with high effect size do not play a major role in ALS pathogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Dipeptidil Peptidases e Tripeptidil Peptidases
/
Estudo de Associação Genômica Ampla
/
Variações do Número de Cópias de DNA
/
Esclerose Lateral Amiotrófica
/
Proteínas de Membrana
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article