Gene linked to depression, and largest genetic study launched

Researchers have identified a gene variant that increases the risk of depression, while elsewhere the largest genetic study for risk factors gets underway.

While the risk of depression has a strong genetic basis, until now research has identified few genetic or biochemical markers. By investigating a socially isolated population in the Netherlands, variants of the NKPD1 gene have now been linked to symptoms of depression.

'We are the first to show a possible genetic connection in this respect,' said Dr Najaf Amin from the Erasmus University Medical Center and lead researcher on the study, published in Biological Psychiatry.

The team of researchers, from the Erasmus University Medical Center in the Netherlands and the Russian Academy of Sciences, performed whole exome sequencing on nearly 2000 genetic samples taken from the Erasmus Rucphen Family study. This study investigated families and descendants from, what was until recently, a socially isolated village with a population of 3000 people in the Netherlands. The genetic isolation within this group increases the presence of rarely-occurring variants and the opportunity to identify them.

By comparing the results of a self-reported questionnaire with genetic data, the study showed that variants in the NKPD1 gene accounted for a four percent increase in the risk of depressive symptoms. This finding was then replicated in a sample from the general population, but here increased depression was associated with different NKPD1 gene variants.

NKPD1 is thought to be involved in the production of sphingolipids, a class of lipids that have been associated with depression and proposed as a therapeutic target.

This genetic discovery coincides with the recent launch of the largest international genome-wide association study (GWAS) to date designed to find more genes that may contribute to the risk of clinical depression and in turn, provide therapeutic targets.

The Australian Genetics of Depression Study aims to collect both self-reported information using an online survey and saliva samples from 20,000 Australians who have – or who have a history of – clinical depression. The international study will eventually collect samples and information from 200,000 participants.

'All the known medications that we've got are working on fairly limited knowledge of the biochemistry behind susceptibility to depression, so what GWAS does is lay bare all of the different pathways that are involved,' Professor Nick Martin of QIMR Berghofer Medical Research Institute, Brisbane and leader of the Australian arm of the collaboration, told the Australian Associated Press.

'Identification of the genes that predispose people to clinical depression could revolutionise future research into causes, treatment and prevention of the illness', Professor Martin said.