Genetic risk profiles for depression and anxiety in adult and elderly cohorts

Abstract

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples.

Figure 1

Percentage of variance explained by genetic risk scores in Rotterdam Study. Percentage of variance represented as difference in Nagelkerke R² after adjustment for age and sex. (a) Analyses based on comparison of DD persons (n=178) to persons scoring in the lowest quartile of CES-D (CES-D=‘0') scale and who did not report any depressive complaints during the follow-up (n=915). (b) Analyses based on comparison of persons with anxiety disorder (n=222) to persons scoring in the lowest quartile of HADS-A (HADS-A=‘0') scale and who did not report any depression or anxiety symptoms during the follow-up (n=290). ^*P value <0.05, ^**P value <0.001.

Figure 2

Percentage of variance explained in depression and anxiety symptoms in ERF study by the genetic risk scores. Percentage of variance represented as difference in R² after adjusting for age sex and family relations. (a–c), analyses of continuous scales. ^*P value <0.05, ^**P value <0.01.

Figure 3

Predicting height (a) and IOP (b) in ERF study. Linear regression analysis of height and intraocular pressure. Percentage of variance represented as difference in R² after adjusting for age sex and family relations.