Ole A. Andreassen
Findings of a genome-wide association study published in JAMA Psychiatry suggest that many overlapping genetic risk variants exist between BMI and schizophrenia, bipolar disorder and major depression.
“Patients with bipolar disorder and major depression have a genetic risk for increased body mass which, together with diet/lifestyle and medication, can explain the increased weight that many patients experience,” Ole A. Andreassen, MD, PhD, of the Institute of Clinical Medicine at the University of Oslo in Norway, told Healio Psychiatry. “In schizophrenia, on the other hand, the large problem many patients are experiencing with weight gain seems to be due to nongenetic effects, such as lifestyle and medication. In fact, people with schizophrenia have a genetic susceptibility to be thinner, which is in line with observations from nontreated patients.”
According to Andreassen and colleagues, genetic studies have highlighted a relationship between BMI and major psychiatric disorders, with increased weight associated with treatment response across these disorders. To determine the extent of overlap between BMI and major psychiatric disorders, as well as to identify genetic loci shared between them, the researchers analyzed data from genome-wide association studies. Specifically, they focused on statistics on BMI, schizophrenia, bipolar disorder and major depression using a conditional false discovery rate statistical framework. Data were available for 1,380,284 participants.
The researchers found that the genetic correlation between BMI and major psychiatric disorders varied. BMI shared 63, 17 and 32 loci with schizophrenia, bipolar disorder and major depression, respectively, that were analyzed at conjunctional false discovery rate less than 0.01, the researchers noted. Further, 34% of the shared loci in schizophrenia, 52% in bipolar disorder and 57% in major depression had risk alleles associated with higher BMI. The rest had opposite directions of associations. According to functional analyses, the overlapping loci are involved in several pathways including intracellular processes, neurotransmitter signaling and neurodevelopment. Loci with opposite and concordant association directions were related mostly to different pathways, the researchers wrote.
“These results provide new insight into the link between body and brain and show an unexpected high number of overlapping genetic risk factors,” Andreassen said. “Further, they demonstrate that mental and body traits are interrelated and can form the basis for future experimental studies identifying the functional mechanisms involved. Second, it was a surprise that schizophrenia risk variants mainly protected against increased BMI, while the opposite effect direction was observed for bipolar disorder and major depression.” – by Joe Gramigna
Disclosures: Andreassen reports grants from the Research Council of Norway, the Kristian Gerhard Jebsen Foundation and South-Eastern Norway Regional Health Authority; personal fees from Lundbeck; consultant fees from HealthLytix and a pending patent application about systems and methods for identifying polymorphisms. Please see the study for all other authors’ relevant financial disclosures.