Identification of blood eQTLs in older adults

Abstract

Genome-wide association studies (GWAS) have been successful in identifying genetic variation associated with a wide range of phenotypes. However, more detailed knowledge of their functional significance is required to provide insights into the molecular mechanisms involved. Single Nucleotide Polymorphisms (SNPs) that influence gene expression (Expression Quantitative Trait Loci-eQTLs) may be one such functional mechanism. As gene expression may change over the lifespan, it is important to identify eQTLs for specific age groups. In this study, we aimed to identify blood eQTLs in older adults. Peripheral blood was collected from participants of the Sydney Memory and Ageing Study (Sydney MAS, N = 445, mean age ± SD = 83.38 ± 4.31) and RNA extracted. Gene expression and SNP genotyping were assessed using arrays. Genome-wide eQTL analyses were undertaken using linear mixed-models. Replication was undertaken in the Older Australian Twins Study (OATS, N = 283, mean age = 75.86 ± 5.28). In the discovery cohort (Sydney MAS), a total of 10,468 unique eQTLs were identified influencing the expression of 1402 probes (1229 genes). A total of 6554 eQTLs were replicated in OATS, out of the 7339 that were available for analysis. We have identified, replicated, and described a catalogue of blood eQTLs in older adults. Noting that replication of these results in independent samples of older adults is required given our modest sample size. However, this information will be a useful resource for further studies, particularly in assessing the potential functions of SNPs identified in GWAS focussing on age-related traits.