rs10237317 (AUTS2): Body Composition and Bipolar

Key takeaways

• rs10237317 is located in the AUTS2 (Autism Susceptibility Candidate 2) gene region and was captured in large-scale genome-wide association studies of body composition and bipolar disorder subphenotypes
• A genome-wide association study of body surface area in more than 330,000 UK Biobank participants identified 456 independent loci linked to adipogenesis and metabolism
• A meta-analysis of waist-to-hip ratio adjusted for body mass index in nearly 695,000 individuals of European ancestry identified 346 loci, with effects generally stronger in women
• People in the top 5% for fat-distribution-increasing allele burden were 1.62 times more likely to exceed metabolic syndrome thresholds compared to the bottom 5%
• A separate genome-wide study of seasonal versus non-seasonal manic episodes in bipolar disorder examined circadian-related subphenotypes in approximately 1,000 cases and controls

What the research says A genome-wide association study of body surface area (BSA) in over 330,000 European-ancestry individuals from the UK Biobank identified 456 conditionally independent variants mapping to genes with known roles in adipogenesis and metabolism, finding BSA to be highly genetically correlated with obesity-related phenotypes and showing that BSA has a causal effect on some downstream diseases through Mendelian randomization analyses. A large meta-analysis of waist-to-hip ratio adjusted for body mass index (WHRadjBMI, a measure of fat distribution independent of overall body size) in 694,649 individuals identified 346 associated loci and 463 independent signals explaining 3.9% of phenotypic variance, with heritability and variant effects generally stronger in women and 92.4% of all sex-dimorphic signals showing stronger effects in women than in men. A genome-wide association study of seasonal versus non-seasonal patterned manic episodes in bipolar disorder examined circadian-related subphenotypes using data from 1,001 cases and 1,033 controls, identifying suggestive signals near the NF1A gene on chromosome 1p31 as the top result (P = 3.08 x 10-7, odds ratio = 2.27).

Reported associations

• Body surface area: A GWAS in 330,000+ European individuals identified 456 independent loci for BSA mapped to adipogenesis and metabolism genes; BSA was genetically correlated with obesity phenotypes, significantly associated with all studied anthropometry parameters, phenotypically associated with 13 chronic diseases, and genetically associated with 6 diseases
• Waist-to-hip ratio adjusted for BMI (WHRadjBMI): A 694,649-person meta-analysis identified 346 loci (463 independent signals) explaining 3.9% of phenotypic variance in fat distribution; the top 5% of allele-burden carriers were 1.62 times more likely to have WHR above metabolic syndrome thresholds compared to the bottom 5%
• Sex-dimorphic fat distribution: Of all identified sex-dimorphic WHRadjBMI signals, 92.4% showed stronger effects in women than in men; about 29% of women-specific index variants were significantly sex-dimorphic versus 14% of men-specific variants
• Seasonal pattern mania in bipolar disorder: A case-only GWAS identified three genomic regions differing between seasonal and non-seasonal patterned manic episodes in bipolar I disorder; the top signal was rs41350144 in the NF1A gene region on chromosome 1p31, reaching suggestive but not genome-wide significance

Evidence quality The two body composition studies are large and well-powered: the BSA GWAS included more than 330,000 UK Biobank participants, and the WHRadjBMI meta-analysis combined UK Biobank and GIANT consortium data from 694,649 individuals, using a genome-wide significance threshold of P < 5 x 10-9 to account for SNP density, with SNP-based heritability estimated at 17.4% overall. The bipolar disorder GWAS was substantially smaller (1,001 cases, 1,033 controls), and its top finding fell below standard genome-wide significance thresholds, placing it in the preliminary and suggestive category. None of the provided study excerpts explicitly name rs10237317 or report its specific effect size, allele frequency, or direction of effect for any phenotype, which limits interpretation specific to this variant.

Lifestyle considerations No lifestyle considerations on file for this variant.