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Depression: Novel Gene Variants Identified

Megan Brooks
April 24, 2018

Researchers have uncovered 17 genetic variants linked to different depression-related phenotypes in a large genome-wide association study, including variants near genes involved in neurotransmission and synapse function.

"This study identifies genes that potentially increase our risk of depression, adding to the evidence that it is partly a genetic disorder," first author David Howard, PhD, Center for Clinical Brain Sciences, University of Edinburgh, United Kingdom, said in a statement.

"The findings also provide new clues to the causes of depression, and we hope it will narrow down the search for therapies that could help people living with the condition," he added.

The study was published online April 16 in Nature Communications.

Blame the Parents?

Investigators analyzed data from 322,000 participants in the UK Biobank, a research database containing health and genetic information on more than half a million people.

The UK Biobank cohort has been extensively phenotyped, allowing the researchers to derive three depression phenotypes: self-reported past help-seeking for problems with nerves, anxiety, tension, or depression (termed "broad depression"); self-reported depressive symptoms with associated impairment (termed "probable MDD"); and major depressive disorder (MDD), identified from International Classification of Diseases (ICD)?9- or ICD-10-coded hospital admission records (termed "ICD-coded MDD").

The researchers identified 17 variants (14 novel) with genome-wide significance across the three depression phenotypes. Fourteen variants were linked to broad depression, two were associated with probable MDD, and one was associated with ICD-coded MDD.

In a replication study, 16 of the 17 variants had an effect in the same direction as that seen in data from a previous genome-wide association study of major depression using research participants from the personal genetics company 23andMe. In a meta-analysis, all 17 variants remained significant.

Genes located near the identified variants are "enriched in excitatory neurotransmission, mechanosensory behavior, post synapse, neuron spine and dendrite functions," the researchers report.

"Our research provides further evidence that the genes we inherit from our parents can influence our risk of developing depression at some point in our lives," Howard told Medscape Medical News.

"The results confirm that there isn't just one gene for depression. Instead, it appears as though there may be many hundreds of small changes in the genetic code that contribute to risk," he added.

This research, he said, has provided clues to the parts of the brain involved in depression, specifically, the connections that exist between nerve cells, or synapses.

"The genetic changes identify chemicals in the body for which we can design drugs that we hope will be more effective in people with the disorder," said Howard.

The study had no commercial funding. The authors have disclosed no relevant financial relationships.

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SOURCE: Medscape, April 24, 2018. Nat Comm. Published online April 16, 2018.

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