Polymorphisms in LMNA and near a SERPINA gene cluster are associated with cognitive function in older people

A recent genome-wide association (GWA) study of late-onset Alzheimer's disease (LOAD) identified 15 novel single nucleotide polymorphisms (SNPs) independent of ApoE We hypothesised that variants associated with LOAD are also associated with poor cognitive function in elderly populations We measured additive associations between the five most strongly associated LOAD SNPs and grouped Mini Mental State Examination (MMSE) scores Variants were genotyped in respondents (mean age 79 years) from the Oxford Healthy Ageing project (OHAP) and other sites of the MRC Cognitive Function and Ageing Study (MRC-CFAS) In adjusted ordinal logistic models, two variants were associated with poorer cognitive function rs11622883 (OR=1.14, 95% CI 1 01-1 28, p=0 040) and rs505058 (OR=1.29. 95% CI 1 02-1 64, p=0 036). These SNPs are close to a SERPINA gene cluster and within LMNA, respectively The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment (C) 2008 Elsevier Inc All rights reserved