A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer's disease risk.
Hum Mol Genet
; 22(4): 816-24, 2013 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-23148125
ABSTRACT
We assessed the role of rare copy number variants (CNVs) in Alzheimer's disease (AD) using intensity data from 3260 AD cases and 1290 age-matched controls from the genome-wide association study (GWAS) conducted by the Genetic and Environmental Risk for Alzheimer's disease Consortium (GERAD). We did not observe a significant excess of rare CNVs in cases, although we did identify duplications overlapping APP and CR1 which may be pathogenic. We looked for an excess of CNVs in loci which have been highlighted in previous AD CNV studies, but did not replicate previous findings. Through pathway analyses, we observed suggestive evidence for biological overlap between single nucleotide polymorphisms and CNVs in AD susceptibility. We also identified that our sample of elderly controls harbours significantly fewer deletions >1 Mb than younger control sets in previous CNV studies on schizophrenia and bipolar disorder (P = 8.9 × 10(-4) and 0.024, respectively), raising the possibility that healthy elderly individuals have a reduced rate of large deletions. Thus, in contrast to diseases such as schizophrenia, autism and attention deficit/hyperactivity disorder, CNVs do not appear to make a significant contribution to the development of AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Duplicação Gênica
/
Variações do Número de Cópias de DNA
/
Doença de Alzheimer
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido