Genetics casts doubt on bidirectional depression, diabetes association
medwireNews: A Mendelian randomization analysis supports a direct effect of major depressive disorder (MDD) on type 2 diabetes risk, but produces no evidence for the reverse scenario.
Susanna Larsson (Karolinska Institutet, Stockholm, Sweden) and co-researchers say that this is in line with observational findings, which are broadly consistent for the effect of depression on cardiometabolic disease, but “inconclusive” as to whether these conditions conversely lead to depression.
As reported in Diabetologia, the team considered 89 single nucleotide polymorphisms (SNPs) with an established association with the risk for MDD. They found that as people’s chances of developing MDD increased, based on their genetic liability, so too did their chances of having type 2 diabetes.
The association was significant, albeit attenuated, after adjusting for BMI, indicating that it “was not completely mediated or biased by” bodyweight, say the researchers.
And their leave-one-out analysis found no single SNP that accounted for the majority of the association.
The team suggests that a “series of biological abnormalities related to depression, including increased counter-regulatory hormone release and activity, alterations in glucose transport function and increased immunoinflammatory activation, may influence the risk of type 2 diabetes.”
Higher genetic liability for MDD, this time based on 90 SNPs, was also associated with a higher likelihood of developing coronary artery disease (CAD). However, the association with heart failure was smaller and only significant in two of the four models used.
“Notably, diabetes and CAD have been proposed as risk factors for heart failure, and CAD can explain more than 60% of heart failure cases,” write Larsson and team.
“Thus, the suggestive association between MDD and heart failure might be partly mediated via type 2 diabetes and CAD.”
The team then looked at the reverse situation, using 184 SNPs with a role in the risk for type 2 diabetes, but found no association with the likelihood of developing MDD. Neither did CAD or heart failure (based on 37 and 10 SNPs, respectively) appear to have a causal role in MDD risk.
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