New gene variants in depression

May 13, 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.

The first author of the study, David Howard, Center for Clinical Brain Sciences, University of Edinburgh, United Kingdom, said that this study identified genes that potentially increase our risk of depression, adding to the evidence that depression is partly a genetic disorder. The new findings would also provide new clues to the causes of depression, and it is hoped the study will narrow down the search for therapies that could help people living with the condition,” he added.

The study was published online April 16, 2018, in Nature Communications.

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:

  • broad depression (self-reported past help-seeking for problems with nerves, anxiety, tension, or depression,
  • probable MDD(self-reported depressive symptoms with associated impairment), and
  • ICD-coded MDD(major depressive disorder (MDD), identified from International Classification of Diseases (ICD)‒9- or ICD-10-coded hospital admission records.

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. They also state the 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. 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.

This research provides clues to the parts of the brain involved in depression, specifically, the connections that exist between nerve cells, or synapses and might identify chemicals in the body for which one day drugs might be designed that more targeted and effective in people with the depression based on the personal genetic outfit of each single patient.

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About the Author
thassodotcom Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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