Original Article Analysis of Genome-Wide Association Study (GWAS) outputs looking for new and novel Alzheimer’s disease (AD) candidate genes
Hui Shi, Christopher Medway, James Bullock, Kristelle Brown, Noor Kalsheker, Kevin Morgan
Division of Clinical Chemistry, Institute of Genetics, School of Molecular Medical Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
Received July 2, 2009; accepted November 8, 2009; available online November 15, 2009
Abstract: We have performed cross-platform comparisons of output from 4 GWAS in late-onset Alzheimer’s disease (LOAD) -- Reiman et al, Li et al, Beecham et al and Carrasquillo et al to search for new association signals. To select genes that might merit further study all SNPs with p-values ranging between 5x10-5 - 5x10-8 from each study were assessed across the other studies (either directly or by using a proxy when comparing data from different chip platforms). This revealed two putative AD candidate genes -tripartite motif-containing protein 15 (TRIM15) and Cytochrome P450 7B1 (CYP7B1). SNP rs929156 (TRIM15) showed suggestive association with LOAD giving a p-value of 1.69X10-5 (Beecham et al), and a p-value = 0.04 (Carrasquillo et al). The odds ratios were consistent across studies indicating an association with risk (OR: 1.1 - 1.5). SNP rs11998077 (CYP7B1) showed a suggestive association with LOAD giving a p-value of 4.59X10-5 (Li et al) and a p-value = 0.006 (Reiman et al). The SNP odds ratios were consistent for this SNP and were protective (OR 0.6 - 0.9). This approach could identify novel LOAD candidate genes for future intensive investigation e.g. deep resequencing to determine if multiple rare variants in these genes associate with disease. (IJMEG907001).
Key words: Late-onset Alzheimer’s disease (LOAD), meta-analysis, genome-wide association analysis (GWAS), tripartite motif-containing protein 15 (TRIM15) gene, replication, single nucleotide polymorphism (SNP)
Address all correspondence to: Kevin Morgan, PhD Division of Clinical Chemistry, Institute of Genetics, School of Molecular Medical Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK. E-mail: Kevin.Morgan@nottingham.ac.uk