Obsessive–compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D₁ and D₂ type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index.

Previous reports have suggested a high prevalence of overweight and obesity among individuals with posttraumatic stress disorder (PTSD). Few studies, however, systematically analyze the relationship between PTSD and body mass index (BMI). We conducted a systematic review and meta-analysis aimed at estimating the association between PTSD and BMI. Fifty-four articles were reviewed, 30 of which (with 191,948 individuals with PTSD and 418,690 trauma-exposed individuals or healthy controls) were eligible for inclusion in the meta-analysis. The pooled standard mean difference, based on a random-effects model, was 0.41 (95% confidence interval, 0.28–0.54; z = 6.26; p < .001). Statistical heterogeneity between the included studies was high (p < .001; I² = 99%). Despite limitations, the findings of this systematic review and meta-analysis suggest an association between PTSD and BMI. Furthermore, longitudinal studies tentatively indicate that PTSD may lead to an increase in BMI and, as such, to the development of overweight/obesity, particularly in women. Further prospective studies and research elaborating the nature and etiology of the association are required.

Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome sequencing in bipolar disorder. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment, including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, FKBP2, RASGRP1, FURIN, FES, MED24 and THRA among others in bipolar disorder. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of bipolar disorder polygenic risk scores across diverse populations and present a high-throughput fine-mapping pipeline.