A genome-wide association study for late-onset Alzheimer's disease using DNA pooling
Tóm tắt
Late-onset Alzheimer's disease (LOAD) is an age related neurodegenerative disease with a high prevalence that places major demands on healthcare resources in societies with increasingly aged populations. The only extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene. In order to identify additional genetic risk loci we have conducted a genome-wide association (GWA) study in a large LOAD case – control sample, reducing costs through the use of DNA pooling.
DNA samples were collected from 1,082 individuals with LOAD and 1,239 control subjects. Age at onset ranged from 60 to 95 and Controls were matched for age (mean = 76.53 years, SD = 33), gender and ethnicity. Equimolar amounts of each DNA sample were added to either a case or control pool. The pools were genotyped using Illumina HumanHap300 and Illumina Sentrix HumanHap240S arrays testing 561,494 SNPs. 114 of our best hit SNPs from the pooling data were identified and then individually genotyped in the case – control sample used to construct the pools.
Highly significant association with LOAD was observed at the
For 109 SNPs outside the
rs727153 lies 13 kb from the start of transcription of lecithin retinol acyltransferase (phosphatidylcholine – retinol O-acyltransferase,
We have validated the pooling method for GWA studies by both identifying the
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