Study in the Netherlands links gene to depression

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A gene has been linked to depression in a study in the Netherlands that researchers hope will shed light on the little-understood condition, reports The Independent.

To investigate the mental illness which affects over 300m people worldwide, researchers studied the genetic makeup of a group of almost 2,000 people in an isolated village in the southwest Netherlands.

The teams at the Erasmus University Medical Centre in The Netherlands and the Russian Academy of Sciences in Novosibirsk found that the NKPD1 gene accounted for a 4% rise in the risk of experiencing the symptoms of depression. These include including feelings of worthlessness, a lack of concentration and fatigue.

A person’s genetic make-up is believed to play a role in the likelihood that they will develop the mental illness. However a single gene has not been categorically linked to the condition and environmental factors are also thought to play a part.

The report says the teams sequenced the DNA of participants to make their findings.

The data originated from the Erasmus Ruchpen Family study into 22 families who have been isolated in the Netherlands until recent decades. Their small gene pool therefore amplifies rare variants, including NKPD1. The results were then replicated in a sample of people which represented the general population. However, different variants within the NKPD1 were identified.

“We are the first to show a possible genetic connection in this respect,” co-author Dr Najaf Amin of the Erasmus University Medical Centre is quoted in the report as saying.

He added that he hopes the findings will enable researchers to target depression on a molecular level, and allow the disease to be measured and diagnosed in an objective manner. “NKPD1 may be one such molecular mechanism,” he said.

The findings come after researchers in Australia launched the world’s biggest genetic study into depression. The Australian Genetics of Depression Study hopes that around 20,000 adults in the country will offer a swab of saliva to aid the investigation, the report says.

Background: Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies.
Methods: To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604).
Results: We detected significant association of depressive symptoms with a gene NKPD1 (p = 3.7 × 10−08). Nonsynonymous variants in the gene explained 0.9% of sex- and age-adjusted variance of depressive symptoms in the discovery study, which is translated into 3.8% of the total estimated heritability (h2 = 0.24). Significant association of depressive symptoms with NKPD1 was also observed (n = 1604; p = 1.5 × 10−03) in the independent replication sample despite little overlap with the discovery cohort in the set of nonsynonymous genetic variants observed in the NKPD1 gene. Meta-analysis of the discovery and replication studies improved the association signal (p = 1.0 × 10−09).
Conclusions: Our study suggests that nonsynonymous variation in the gene NKPD1 affects depressive symptoms in the general population. NKPD1 is predicted to be involved in the de novo synthesis of sphingolipids, which have been implicated in the pathogenesis of depression.

Najaf Amin, Nadezhda M Belonogova, Olivera Jovanova, Rutger WW Brouwer, Jeroen GJ van Rooij, Mirjam CGN van den Hout, Gulnara R Svishcheva, Robert Kraaij, Irina V Zorkoltseva, Anatoly V Kirichenko, Albert Hofman, André G Uitterlinden, Wilfred FJ van IJcken, Henning Tiemeier, Tatiana I Axenovich, Cornelia M van Duijn

The Independent report
Biological Psychiatry abstract

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