BIONIC: Biobank Netherlands Internet Collaboration: proof of principle for major depressive disorder (WC2014-053)


Starting date: 01/07/2014

Major depressive disorder (MDD) is a common, heterogeneous burdensome mental disorder. MDD is a genetically complex trait with a heritability of 31-42%. Thus far, the identification of potential loci for MDD has been of limited success. In the largest genome-wide association study (GWAS) of MDD yet conducted, none of the loci reached the set point of genome-wide significance. One reason for the lack of significance is that sample sizes are too small. Complex diseases such as MDD are considered to be caused by a large number of causal variants with small effects. Because most effect sizes associated with genetic markers in psychiatry are fairly small (odds ratios are approximately 1.1 to 1.2), large samples are required to detect significant associations.

Recently, a major breakthrough in the search for single nucleotide polymorphisms (SNPs) for schizophrenia took place. In the updated meta-analyses of GWAS studies, 108 genome-wide significant hits were reported.2 Following the progress of genetic research into these and other disease phenotypes, the collection of larger cohorts is likely to yield success in identifying the genetic variants involved in MDD.

For MDD, an increase in sample size can be realized through recruiting more cases and controls, for which DNA and GWA data will be subsequently collected. This approach is considerably resource-intensive. A complementary and very efficient approach would be to phenotype MDD in existing biobank cohorts, such as those united in BBRMI-NL. In addition to MDD case finding, it is also important to verify that controls have had no MDD in lifetime, given the high lifetime prevalence of MDD (last estimates for the Netherlands 13% in men and 24% in women). Unscreened control groups may contain a high number of cases, which reduces statistical power and thus limits success in gene finding enterprises. Furthermore, previous studies have been highly heterogeneous in their assessment of MDD. Harmonizing MDD assessment throughout studies may result in more homogeneity of MDD between studies, and offers the possibility to study specific characteristics of depression. 

To increase the number of MDD cases and controls and harmonize the assessment of MDD, we will set up a phenotypic assessment of MDD in existing studies with genome-wide data that participate in Biobanking and Biomolecular Research Infrastructure – Netherlands (BBMRI-NL), using a valid online instrument. In addition to the relevance for gene finding in MDD, this will serve as a proof of concept study for the feasibility of a rapid phenotypic assessment in ongoing biobank studies, which may be applied to other phenotypic assessments (e.g. other psychiatric, behaviorial or somatic traits) in the near future.