Extensive polygenic overlap was found between body mass index (BMI) and major psychiatric disorders, including schizophrenia, bipolar disorder, and major depressive disorder (MDD), according to a genome-wide association study (GWAS) results published in JAMA Psychiatry.
Shahram Bahrami, PhD, from the University of Oslo, Norway, and colleagues analyzed independent GWAS data (N=1,380,284) collected between August 2017 and May 2018 from individuals with schizophrenia (n=34,241), bipolar disorder (n=20,352), and MDD (135,458), as well as BMI data (n=795,640). The investigators used a conditional false discovery rate statistical approach to identify genetic loci shared between BMI and major psychiatric disorders, as well as FUMA, a web-based platform used to annotate and interpret GWAS results, to define the independent genomic loci.
The analyses revealed varied genetic correlation between BMI and major psychiatric disorders (schizophrenia: negative; r for genetic, –0.11; P =2.4909×10-10; bipolar disorder: nonsignificant; r for genetic, –0.06; P =.0103; MDD: positive; r for genetic, 0.12; P =6.7040×10-10). Initially, the researchers found 63 shared loci for BMI and schizophrenia, 17 for bipolar disorder, and 32 for MDD at conjunctional false discovery rate <0.01. Of the shared loci, 34% had risk alleles concordantly associated with BMI in schizophrenia, 52% in bipolar disorder and 57% in MDD at conjunctional false discovery rate <0.05.
The overlapping loci were involved in several pathways, including neurodevelopment, neurotransmitter and hormone signaling, and intracellular processes. However, loci with concordant and opposite association directions mostly pointed to different pathways. While most of the genetic variants in schizophrenia were related to weight loss, the genetic risk variants for MDD and bipolar disorder were primarily associated with weight gain.
The findings suggest that factors such as antipsychotic treatment, diet, or lifestyle may contribute to weight gain in patients with long-term disease. The researchers noted that “the current findings of a mixture of association directions for the shared loci underscores the complexity of this genetic relationship and suggest that factors other than disease-specific genetics play a significant role in weight gain in [major psychiatric disorders], particularly in [schizophrenia].”
They concluded, “The findings have implications for the discovery of drugs with fewer adverse events and potential future individualized treatment to reduce weight gain.”
Bahrami S, Steen NE, Shadrin A, et al. Shared genetic loci between body mass index and major psychiatric disorders: a genome-wide association study [published online January 8, 2020]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.4188