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

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, GERAD1 Consortium, Patrick Kehoe

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)816-24
Number of pages9
JournalHuman Molecular Genetics
Volume22
Issue number4
DOIs
Publication statusPublished - 15 Feb 2013

Research Groups and Themes

  • Cerebrovascular and Dementia Research Group

Keywords

  • Aged
  • Alzheimer Disease
  • Amyloid beta-Protein Precursor
  • Case-Control Studies
  • DNA Copy Number Variations
  • Gene Duplication
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome, Human
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Receptors, Complement 3b
  • Risk Factors

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