Women carry a higher genetic risk of depression, a new study has found.
Claiming to be the largest genetic study to date on sex differences in major depression, the research published on Wednesday in Nature Communications has found 16 genetic variants linked to depression in women and eight in men.
The study, led by Australia’s QIMR Berghofer Medical Research Institute, showed a large proportion of the variants associated with depression were shared between sexes, but there was a “higher burden of genetic risk in females which could be due to female-specific variants”.
Dr Brittany Mitchell, a senior researcher at QIMR Berghofer’s genetic epidemiology lab, said “we already know that females are twice as likely to suffer from depression in their lifetime than males”.
“And we also know that depression looks very different from one person to another. Until now, there hasn’t been much consistent research to explain why depression affects females and males differently, including the possible role of genetics.”
The study acknowledged explanations have been put forward spanning behavioural, environmental and biological domains, including men being less likely to seek help leading to under-diagnosis, and environmental exposures such as women being more frequently exposed to sexual abuse and interpersonal violence.
The study stated that together these factors highlight the need for a “multifaceted approach” to understanding the underlying mechanisms of depression but proposed that a “key component of the biological mechanisms underlying these disparities could be differences in genetics”.
The researchers analysed the DNA from five international cohorts – Australia, the Netherlands, United States and two from the United Kingdom – with a final sample size of 130,471 women and 64,805 men with major depression, and 159,521 women and 132,185 men without the diagnosis.
They also found stronger genetic correlations in women between depression and metabolic traits (such body mass index and metabolic syndrome) than in men with the same traits.
Dr Jodi Thomas, the lead researcher, said these genetic differences “may help explain why females with depression more often experience metabolic symptoms, such as weight changes or altered energy levels”.
The authors acknowledged the study included roughly twice as many women with depression as men, and performed additional analyses to ensure their findings were not due to the difference in sample sizes.
They also acknowledged limitations that their analyses were restricted to Europeans only, limiting the applicability of the findings to other populations.
Prof Philip Mitchell, from the School of Clinical Medicine at the University of New South Wales, said “there has been longstanding debate about the reasons for the consistent finding around the world that depression is more common in females than males, with most studies reporting that women have two to three times the risk of depression compared to men”.
“The most dominant theories have been related to social and psychological factors, for example the impact of the female role in caring for families compared to the income earning role of males, or personality vulnerabilities in women,” said Mitchell, who was not involved in the study.
“This very interesting novel genetic study in a very large global study provides strong evidence that these differences in rates of depression may in fact be due to genetic factors, with the statistically significant finding of more depression risk regions in the genome in females compared to males, and little overlap in these regions between males and females.
“As well as strengthening the evidence that the differences in depression rates between men and women may be largely due to biological factors, it also points to the future possibility of different pharmacological treatments for depression in women and men, as the biological systems coded for by these genetic regions become better understood.”
