In what is by far the largest study of its kind focused on major depressive disorder, researchers from Pfizer, Massachusetts General Hospital and 23andMe identified 17 single nucleotide polymorphisms in 15 genetic loci significantly associated with depression among people of European ancestry.
The study may lead to better understanding of the biology of the condition. Major depressive disorder is characterized by mood changes, sleep disruption, fatigue and loss of appetite, and is one of the leading causes of disability and is estimated to affect more than 350 million people worldwide. The study drew on massive amounts of data from 23andMe customers who’ve consented to research and completed online surveys about depression.
“These studies provide evidence for large-scale consumer genomic data as a powerful and efficient alternative complement to data from traditional means of ascertainment for neuropsychiatric disease genomics,” according to the study. “If one reasonable strategy adopted by that study is to develop more precise or refined phenotypes, another is to efficiently identify much larger cohorts for study despite less intensive phenotyping.”
Although researchers have long known that genetics plays an important role in the development of depression, attempts in the past to study the genetics behind the disorder have failed to produce results. One study in 2013 by the Psychiatric Genomics Consortium (PGC) looked at data from more than 17,000 people with depression but couldn’t detect any genetic hits. For a time researchers thought the studies were being confounded by how major depressive disorders were being diagnosed – by basically lumping different forms of depression together – or that the studies were undersized.
Depression is a heterogeneous disease, with many genes contributing to the condition. Environmental influences also play a role in its development. Jonathan Flint, a geneticist at the University of Oxford and a key researcher in the PGC study, concluded that he either needed more data from more individuals to find a signal or a more select group of individuals to study, according to an article in the journal Nature. Flint took the latter strategy studying data from about 10,000 individuals in China, a cohort that was relatively homogenous and had the most severe depression. Last year he and other researchers published their findings, uncovering two variants associated with the condition among people of Han Chinese ancestry, but those variants do not appear to influence the condition in people of European descent.
Another approach would be to find a much larger cohort of individuals and that’s what this latest study has done by tapping into 23andMe’s data from customers. The study includes more than 450,000 customers, who consented to participate in research, about 120,000 of whom reported being diagnosed with depression.
By using 23andMe’s online method and collecting data from a very large group of individuals, the researchers were able to gather enough data to power their study. The sheer volume of data – the number of people, the amount of both phenotypic and genotypic data – allowed the scientists to see signals that they may not have seen otherwise. The variant most strongly associated with depression was found in a gene region involved with brain function. The most statistically significant variant is located between two genes that are expressed in the brain, MEF2C and TMEM161B. MEF2C is involved in the regulation of synapses and studies have associated variants in this gene with epilepsy and intellectual disability.
The remainder of the single nucleotide polymorphisms found to reach genome-wide significance for association with depression were in 13 other genes or gene regions. Many of these are expressed in the central nervous system for neurodevelopment or have been identified in other genome-wide association studies to be related to different psychiatric traits. All of these variants are different than the two variants associated with depression in people of Han Chinese ancestry, but the variants found in both studies may help in the ongoing effort to understand the underlying biology of depression. Researchers hope these new findings will offer a better understanding of the biology of the disease and could help in the search for the right treatments for depression.
This study can be found in the journal Nature Genetics.