background Genome-wide significant findings in genome-wide association studies (gwas) are generally rare and it has been suggested that the effects of single gene variants are even smaller than expected, with odds ratios maybe lower than 1.2. However, other explanations are also possible, including the rare genetic variant hypothesis. Since gwa studies are less suitable to detect the effects of rare genetic variants, knowledge about the genetic architecture of psychiatric disorders is very important.
aim We used genome wide association data to test whether the assumption of a polygenic component for depression holds. A second test involved analysing whether this polygenic component influences anxiety.
methods The risk profile was based on the results of a gwas performed in 1738 cases and 1802 controls from the Netherlands Twin Register (ntr) and the Netherlands Study of Depression and Anxiety (nesda). snps were selected based on variable p-value thresholds, from p-value below 0.0001 to p-value 1. Individual genetic risk scores were evaluated in two samples from the Rotterdam Study comprising 178 cases and 915 controls for depression and 216 cases and 135 controls for anxiety, and from the Erasmus Rucphen Family (erf) study in which symptoms of anxiety and depression were assessed in 1886 participants. A genetic score was calculated for each individual by multiplying the number of risk alleles per snp with the log odds ratio, summed over all snps. Regression analyses were used to investigate whether these scores predicted depression and anxiety.
results The genetic scores explained up to ~1 % of the variance in depression and up to 3.1 % in anxiety in the target samples.
conclusion These findings suggest the presence of many loci, each with a very small effect influencing depression as well as anxiety. Larger scale genome wide association studies might be able to detect these effects.