rs10250407 (CHN2): Body Size Variant with Brain eQTL
Key takeaways
- Identified in a whole-genome sequencing study of over 267,000 people as one of 106 new signals for body size and fat distribution traits
- The ALT allele is linked to reduced WIPF3 gene activity specifically in brain cortex tissue
- Evidence comes from a single large European-ancestry study; variant-specific replication data are not yet reported
- The study covered 12 body measurement traits spanning BMI, height, waist and hip circumference, and measures of fat mass
Key takeaways
- Identified in a whole-genome sequencing study of over 267,000 people as one of 106 new signals for body size and fat distribution traits
- The ALT allele is linked to reduced WIPF3 (WAS/WASL Interacting Protein Family Member 3) gene activity specifically in brain cortex tissue
- Evidence comes from a single large European-ancestry study; variant-specific replication data are not yet reported in the available literature
- The study covered 12 body measurement traits spanning BMI, height, waist and hip circumference, and measures of fat mass
What the research says A whole-genome sequencing and deep imputation study examined 12 anthropometric traits - including body mass index (BMI), height, waist and hip circumference, waist-to-hip ratio, and total and trunk fat mass - in a discovery cohort of 57,129 individuals, with follow-up in 210,823 additional participants of European descent (up to 267,616 total). The study identified 106 previously unreported genome-wide significant signals; of these, 6 were in genomic regions not previously linked to anthropometric traits, 28 were independent signals at already-known regions, and 72 represented signals previously reported for a different anthropometric trait. Tissue-specific expression data from GTEx v11 (953 donors) show that the ALT allele at rs10250407 reduces WIPF3 expression in brain cortex tissue by approximately 0.26 log2 units per allele (p = 3.6e-5, FDR < 0.05) GTEx Portal.
Reported associations
- Anthropometric traits (body size and composition): rs10250407, in the CHN2 locus, was identified as one of 106 new genome-wide significant signals for anthropometric traits in a whole-genome sequencing study of up to 267,616 individuals; the traits examined included BMI, weight, height, waist circumference, hip circumference, waist-to-hip ratio, and fat and lean mass measures, though the specific per-variant effect size and associated trait for the CHN2 locus are not detailed in the provided study excerpts
- WIPF3 brain cortex expression: the ALT allele is associated with reduced WIPF3 expression in brain cortex tissue (approximately 0.26 log2 units per allele, p = 3.6e-5, FDR < 0.05, GTEx v11, 953 donors) GTEx Portal
Evidence quality The anthropometric trait association comes from a large-scale whole-genome sequencing study with a discovery stage of 57,129 individuals and a follow-up stage of 210,823 additional participants of European descent, assessing 15,844,966 sequence variants across 23 cohorts. While the large overall sample size supports the discovery of the 106 new signals collectively, the specific effect size, p-value, and replication status for rs10250407 alone are not available in the provided study text, limiting precision of the evidence summary for this variant specifically. The WIPF3 eQTL evidence is from GTEx v11 (953 donors, cis-window, FDR < 0.05) and represents a tissue-specific mechanistic association in brain cortex; eQTL effects reflect gene regulation, not clinical outcomes, and the relationship between this brain expression effect and the anthropometric trait associations requires further investigation.
Tissue-specific expression effects
- WIPF3: the ALT allele reduces expression in brain cortex tissue by approximately 0.26 log2 units per allele (p = 3.6e-5) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10250407?
rs10250407 is a genetic variant located in the CHN2 locus that was identified as one of 106 newly discovered genome-wide significant signals for body size and fat distribution traits in a large whole-genome sequencing study of over 267,000 people.
What body traits is rs10250407 associated with?
The variant was identified in a study examining 12 anthropometric traits including BMI, height, waist and hip circumference, and fat mass measures. The specific trait and per-variant effect size for this locus alone are not detailed in the currently available study excerpts.
What does GTEx show for rs10250407?
GTEx v11 data from 953 donors show that the ALT allele of rs10250407 is associated with reduced WIPF3 gene expression in brain cortex tissue. This is a tissue-specific gene regulation effect and does not directly indicate a clinical outcome.
How large was the study that found rs10250407?
The study used a discovery cohort of 57,129 individuals with follow-up in 210,823 additional participants, totaling up to 267,616 people of European descent, assessing over 15.8 million sequence variants across 23 cohorts.
Is the evidence for rs10250407 well replicated?
The 106 signals were discovered in a large multi-cohort design with distinct discovery and follow-up stages. However, variant-specific effect sizes and replication data for rs10250407 alone are not described in the available study text, so the individual signal should be considered preliminary.