rs115862987 (COBLL1): Body Shape and Fat Distribution

Key takeaways

• rs115862987 is a genetic variant studied in the context of body fat distribution, located in the COBLL1 gene region
• A genome-wide association study (GWAS) of more than 400,000 UK Biobank participants identified multiple novel genetic loci for body shape using measures that account for both height and BMI
• Body-shape genetic signals differ between women and men, with some loci unique to each sex
• Allometric body-shape measures that account for height reveal up to two thirds of genetic loci not previously seen with traditional BMI-adjusted measures
• Genes linked to body shape in this research area overlap with pathways for morphogenesis (the biological process controlling body structure development), organogenesis (organ formation), and cancer

What the research says

A genome-wide association study by Christakoudi et al. (Scientific Reports, 2021) examined genetic variants associated with allometric body-shape indices in 219,872 women and 186,825 men of white British ancestry from UK Biobank, using Bayesian linear mixed-models (BOLT-LMM, a statistical approach well-suited to large biobank datasets). The study evaluated A Body Shape Index (ABSI, a waist-based measure), Hip Index (HI), and a Waist-to-Hip Index (WHI), all calibrated to be mathematically independent of both height and body mass index (BMI, a ratio of weight to the square of height), contrasting with traditional indices that adjust only for BMI. The most prominent genome-wide signal across all indices was rs72959041 in RSPO3, a gene expressed in visceral adipose tissue (fat surrounding internal organs) that regulates adrenal cell renewal.

Reported associations

• Body shape (waist measure, ABSI): Genome-wide signals for A Body Shape Index included region-specific loci in VEGFA and HMGA1 in women, and in C5orf67 and HOXC4/5 in men
• Hip circumference distribution (HI): Hip Index showed genome-wide associations with KLF14 in women, and with RSPO3, VEGFA, and SLC30A10 in men
• Visceral adipose tissue and adrenal function: The top variant overall, rs72959041 in RSPO3, is expressed in visceral adipose tissue and involved in adrenal cell renewal
• Morphogenesis and cancer-related pathways: Genes ranking highly across body-shape indices included those involved in morphogenesis and organogenesis, categories that overlap substantially with genes previously linked to cancer development and progression

Evidence quality

Christakoudi et al. (Scientific Reports, 2021) conducted one of the largest GWAS of allometric body-shape indices to date, with over 400,000 UK Biobank participants analyzed using BOLT-LMM. Conducting separate analyses in women and men appropriately addressed documented sexual dimorphism (biological differences between sexes) in body-shape genetics, where associations were fewer in men. The allometric indices used differ from traditional measures in also accounting for height, which the authors propose explains why one to two thirds of identified loci were novel compared to prior GWAS Catalog entries for traditional body-shape indices. The available study text does not report specific p-values or effect sizes for rs115862987 individually; the associations described above reflect general findings across the study population. No replication cohort data or conflicting findings were described in the provided excerpts.

Lifestyle considerations

No lifestyle considerations on file for this variant.