A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer%26apos;s disease risk

作者：Chapman Jade; Rees Elliott; Harold Denise; Ivanov Dobril; Gerrish Amy; Sims Rebecca; Hollingworth Paul; Stretton Alexandra; Holmans Peter; Owen Michael J; ODonovan Michael C; Williams Julie^*; Kirov George

来源：Human Molecular Genetics, 2013, 22(4): 816-824.

DOI：10.1093/hmg/dds476

We assessed the role of rare copy number variants (CNVs) in Alzheimers 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 Alzheimers 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.

• 出版日期2013-2-15