rs11624704 (NRXN3): Waist-to-Hip Ratio Variant

Key takeaways

• rs11624704 near NRXN3 reached genome-wide significance for waist-to-hip ratio in a genome-wide association study
• The association was specific to waist-to-hip ratio as a continuous measure, not to obesity as a binary outcome or overall body weight
• The same study found that FTO gene variants drove the primary signal for obesity as a binary trait, while NRXN3 did not
• Evidence comes from one study using extreme BMI phenotypes; independent large-scale replication is not documented in the available literature

What the research says A GWAS examining extreme obesity phenotypes found rs11624704, near NRXN3 (neurexin 3), significantly associated with waist-to-hip ratio (WHR) at P = 2.67×10^-9 in a discovery sample of 520 severely obese cases (BMI > 35 kg/m²) and 540 never-overweight controls (BMI < 25 kg/m²), with follow-up genotyping in 2,256 total individuals. The same study identified FTO gene variants as the primary signal for obesity as a binary trait, while this locus showed genome-wide significance only for the continuous WHR measure. The authors noted prior associations between this variant and body weight and fat distribution in the literature, though those source studies are not included here.

Reported associations

• Waist-to-hip ratio: Genome-wide significant association (P = 2.67×10^-9) in a case-control GWAS using extreme BMI phenotypes (n = 520 cases BMI > 35 kg/m², n = 540 controls BMI < 25 kg/m²; follow-up genotyping n = 2,256)
• Body weight and fat distribution: Referenced as prior associations in the study text; the original source studies are not included in the provided literature

Evidence quality The evidence for this variant rests on a single study that used extreme-phenotype ascertainment - severely obese cases and never-overweight controls - to boost statistical power in a relatively small discovery cohort of approximately 1,060 individuals. Follow-up genotyping extended to 2,256 individuals including family members; not all participants were independent replication samples. The association with WHR crossed the genome-wide significance threshold at P = 2.67×10^-9. The authors themselves note the relatively small sample size while observing that extreme phenotype ascertainment can increase detection power; no independent large-scale replication in population-based cohorts is documented in the available literature. No conflicting findings are present among the provided studies.

Lifestyle considerations No lifestyle considerations on file for this variant.