Genetic analysis of Alzheimer's disease in the Uppsala Longitudinal Study of Adult Men

Abstract

Background/aims: Genetic factors influencing common complex conditions have proven difficult to identify, and data from numerous investigations have provided incomplete conclusions as to the identity of these genes. Here we aimed to identify susceptibility genes for late-onset Alzheimer's disease (AD).

Methods: The case-control analysis included samples from 86 AD patients and 404 cognitively healthy controls selected from the Uppsala Longitudinal Study of Adult Men (ULSAM). In the incidence analysis, all 1,088 genotyped ULSAM participants were included. DNA samples from ULSAM participants were analyzed for 2,578 single nucleotide polymorphisms (SNP) within 368 genes. The selection of genes tested for association to AD within this cohort was based on genes previously implicated in conditions with relevance to ULSAM, such as dementia, cardiovascular disease, diabetes and metabolic syndrome, osteoporosis, and cancer.

Results/conclusion: Association analysis revealed 82 genes containing at least 1 significant SNP at p < 0.05 with association to AD. Only 20 genes remained significant after a permutation test to correct for multiple comparisons within individual genes. Using publicly available data from 2 genome-wide association (GWA) studies and linkage disequilibrium data from HapMap, we attempted to replicate the AD association identified in ULSAM. In addition to apolipoprotein E, we were able to replicate 5 other genes in both GWA studies at p < 0.05.