Genetic variation at the IL1RAP locus and its influence on late-life

Abstract

Title: Genetic variation at the IL1RAP locus and its influence on late-life depression in a population-based sample in Gothenburg, Sweden Author: David Mårdensjö Supervisor: Anna Zettergren, PhD Introduction: Recently, it was discovered in two large genome-wide association studies that there is an association between genetic variation in the gene interleukin-1 receptor associated protein (IL1RAP) and Alzheimer’s disease traits. Inflammation has been implicated as an important pathomechanism for both dementia and late-life depression (LLD). However, the association between ILRAP and LLD have to our knowledge never been specifically investigated Aim: The aim of this study was to examine the possible association between LLD and genetic variation in, or in close vicinity, to the gene IL1RAP in a population-based sample of older individuals. Methods: Genotype data were available for 3,559 study participants from four cohorts of the longitudinal gerontological and geriatric population studies in Gothenburg, and 2715 were included in the statistical analysis after exclusion. All participants took part in a neuropsychiatric and neuropsychological examination. The relation between genotype and depression diagnoses as well as with the severity of depressive symptoms (measured with MADRS-score) were investigated. Results: The main findings were associations between the common homozygotes of rs3773976, rs12053868, rs3773970 and rs4687151, and females with major depression, with the strongest being for rs3773970 (OR: 2.01 [95% CI: 1.14-3.56], p=0.016) in the logistic regression model adjusted for APO e4-status and age at first interview. Significant associations between the common homozygotes of two of these polymorphisms (rs3773976 and rs3773970) and increased MADRSscore were also found in the linear regression model using the same covariates. No association was found for rs9877502. Conclusions: Our results indicate that genetic variation at the ILRAP locus may be of importance for LLD. However, the effect size and study sample were small. The finding should be interpreted with caution until replicated in additional samples of older indviduals. Key words: Late-life depression, gene, interleukin 1 receptor accessory protein