Two gene variants have been linked to major depressive disorder by an international research consortium.
'Major depressive disorder, one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis,' said Professor Jonathan Flint of Oxford University, who led the study. However, no genetic variants have been robustly replicated in over 9000 studies.
The team analysed over six million SNPs, or gene variants, in the genomes of just over 10,000 Han Chinese women, 5303 of whom had been diagnosed with severe depression. They identified two gene variants – located in the SIRT1 and LHPP genes – which were strongly linked to depression.
Previous studies involving greater numbers had come up empty, so the team was taken by surprise by the strength of their results. 'I thought, there's no way,' Professor Flint told Nature News.
Where other studies had included diverse populations, the CONVERGE team recruited a very homogenous group of people. Their study population consisted of Han Chinese women between ages 30 and 60 years who had had at least two episodes of major depressive disorder. By being so specific in choosing their population, the team hoped to recruit a group of people with a very similar form of depression.
Depression is believed to consist of a group of disorders that have similar symptoms but different underlying causes. Previous studies could have missed genetic associations because they included a mixed bag of depression disorders, diluting the effects.
The team replicated their results in further group of about 6000 Chinese men and women, showing that the results are not gender specific. However, while the two gene variants are very common in the Chinese population, they are relatively rare in European populations.
Of the two gene variants, one is located in a gene (SIRT1) that plays an important role in mitochondria, which produce energy in our cells. 'It's an appealing bit of biology for a disorder that makes people tired and unmotivated,' Dr Douglas Levinson of Stanford University, who was not involved in the study, told Nature News. The function of the second gene (LHPP) is still unclear.
The team predicts that their discovery will lead to more gene variants being found for depression. They also hope the findings will provide insights into the mechanisms that underlie depression and help identify new drug targets or prevention strategies.