15 genomic regions associated with depression uncovered

Written by Sonia Mannan

A genomic study using data from 23andMe (CA, USA) has identified 15 genomic regions that may be associated with depression in individuals of European descent. The results of the study were published in the journal Nature Genetics.
“Identifying genes that affect risk for a disease is a first step towards understanding the disease biology itself, which gives us targets to aim for in developing new treatments,” explained co-author Roy Perlis (Massachusetts General Hospital, MA, USA). “More generally, finding genes associated with depression should help make clear that this is a brain disease, which we hope will decrease the stigma still associated with these kinds of illnesses.”

Although there is the strong evidence supporting the heritability of depression, previous genome-wide studies were unable to identify variants influencing the risk for depression in individuals of European descent. 23andMe provided report data from 75,607 individuals diagnosed with clinical depression and 231,747 individuals with no history of depression.

This resulted in the identification of two genomic regions; one containing a poorly understood gene that is expressed in the brain and another containing a gene previously associated with epilepsy and intellectual disability, which are associated with depression risk.

A meta-analysis of these results with other genome-wide association study results was performed. The smaller genome-wide association studies involved approximately 9200 individuals with a history of depression and 9500 controls. Possible risk gene sites in samples from another group of results from 23andMe were also used. This consisted of almost 45,800 individuals with depression and 106,000 controls.

After analysis of all three data sets, 17 independent SNPs from 15 genomic regions were identified as being significantly associated with a diagnosis of depression. This included 17 specific sites with some being located in or near genes known to be involved in brain development.

“The neurotransmitter-based models we are currently using to treat depression are more than 40 years old, and we really need new treatment targets. We hope that finding these genes will point us toward novel treatment strategies,” commented Perlis. “Another key takeaway from our study is that the traditional way of doing genetic studies is not the only way that works. Using existing large datasets or biobanks may be far more efficient and may be helpful for other psychiatric disorders, such as anxiety disorders, where traditional approaches also have not been successful.”

The authors hope the results of their study will enable an improvement on the treatment of depression and allow a better understanding of the disorder.

Sources: Hyde CL, Nagle MW, Tian C et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat. Genet. doi:10.1038/ng.3623 (2016) (Epub ahead of print); www.massgeneral.org/about/pressrelease.aspx?id=1969