A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer's disease risk

Year: 2012

Type: article

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.

Source: Human Molecular Genetics

DOI: 10.1093/hmg/dds476

Authors: Jade Chapman, Elliott Rees, Denise Harold, Dobril Ivanov, Amy Gerrish, Rebecca Sims, Paul Hollingworth, Alexandra Stretton, Peter Holmans, Michael J. Owen, Michael C. O'Donovan, Julie Williams, George Kirov

Institution: Cardiff University

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390

Funders: Wellcome Trust, Alzheimer's Society, Bundesministerium für Bildung und Forschung, University College London Hospitals NHS Foundation Trust, H. Lundbeck A/S, National Institutes of Health, Medical Research Council, National Institute on Aging

OpenAlex ID: W2168317986