Expressive

rs10761247 (PHF2): Income and Body Fat Distribution

Key takeaways

  • rs10761247 near PHF2 has been linked to income-related traits in a GWAS of 668,288 Europeans, with small effect sizes and the polygenic index explaining only 1-5% of income variance
  • The same locus was also found in a 694,649-person meta-analysis of body fat distribution, with effects generally stronger in women than men
  • Only about one-quarter of the income polygenic index effect is from direct genetic influences, with the rest tied to shared pathways with education and environment
  • GTEx data shows this variant's alternative allele reduces PHF2 expression in gastrointestinal tissues and alters expression of three other nearby genes across multiple tissue types
  • Both associations come from large studies restricted to European-ancestry populations, limiting generalizability

Key takeaways

  • rs10761247 near PHF2 has been linked to income-related traits in a GWAS of 668,288 Europeans, with small overall effect sizes and the polygenic index explaining only 1-5% of income variance.
  • The same locus was also identified in a meta-analysis of 694,649 individuals as associated with body fat distribution (waist-to-hip ratio adjusted for BMI), with effects generally stronger in women.
  • Only about one-quarter of the income polygenic index effect is from direct genetic influences; the rest reflects shared pathways with education and environment.
  • GTEx data shows this variant's alternative allele reduces PHF2 expression in gastrointestinal tissues and alters expression of three other nearby genes across multiple tissue types.
  • Both associations come from large studies restricted to European-ancestry populations, which limits how broadly the results apply.

What the research says A GWAS meta-analysis spanning 32 cohorts across 12 countries (effective N = 668,288 individuals of European descent) identified 162 genomic loci associated with a common genetic factor underlying multiple income measures, referred to as the Income Factor; effect sizes were uniformly small, with the full polygenic index explaining 1-5% of income variance and only about one-quarter of that traceable to direct genetic effects. A separate meta-analysis of waist-to-hip ratio adjusted for BMI (WHRadjBMI, a measure of where body fat is distributed rather than overall body weight) across 694,649 individuals identified 463 signals in 346 loci, with SNP-based heritability estimated at approximately 25.6% in women versus 16.7% in men, and the top index SNPs together explaining 3.9% of phenotypic variance in an independent validation sample of 7,721 individuals. The Income Factor showed a genetic correlation of 0.92 (s.e. = 0.006) with educational attainment, indicating that income and education share most of their genetic architecture; accounting for that overlap revealed that the remaining income-specific genetic signal was linked to better mental health but reduced physical health and increased risky behaviors such as drinking and smoking.

Reported associations

  • Income (Income Factor): This locus was among 162 identified in a multi-cohort GWAS of 668,288 European-ancestry individuals; SNP heritability for the Income Factor was estimated at 0.07 (s.e. = 0.002), and the polygenic index built from all 162 loci explains roughly 1-5% of income variance, with approximately one-quarter from direct genetic effects.
  • Body fat distribution (WHRadjBMI): This locus was among 463 signals in 346 loci in a meta-analysis of 694,649 individuals for waist-to-hip ratio adjusted for BMI; approximately one-third of all signals were sexually dimorphic, and 92.4% of sex-dimorphic effects were stronger in women. The top-associated index SNPs explain 3.9% of overall phenotypic variance in fat distribution.

Evidence quality Both associations come from large, well-powered meta-analyses. The income study combined 32 cohorts across 12 countries for an effective sample of 668,288; the body fat study merged UK Biobank and GIANT consortium data for 694,649 individuals, with validation in an independent sample of 7,721. Effect sizes are small throughout: the income polygenic index explains 1-5% of income variance, and body fat index SNPs collectively explain 3.9% of phenotypic variance. Both analyses were restricted primarily to individuals of European ancestry, limiting generalizability to non-European populations. The income study explicitly notes that income heritability estimates are not fixed values but vary with social, technological, and institutional conditions across regions and time. Specific per-variant statistics (p-value or beta coefficient) for rs10761247 individually are not reported in the study excerpts provided. There are no conflicting findings between the two studies, as they address entirely separate phenotypes.

Tissue-specific expression effects

  • PHF2: The alternative allele is linked to reduced expression in the esophageal muscle layer (Esophagus_Muscularis) and the S-shaped lower colon (Colon_Sigmoid), meaning modestly lower PHF2 gene activity in two gastrointestinal tissues. GTEx Portal
  • BARX1: The alternative allele is linked to increased expression in the horizontal mid-section of the colon (Colon_Transverse), meaning higher BARX1 gene activity in this part of the large bowel. GTEx Portal
  • ENSG00000289031: The alternative allele is associated with reduced expression in breast tissue (Breast_Mammary_Tissue), meaning modestly lower activity of this gene. GTEx Portal
  • FAM120AOS: The alternative allele is linked to increased expression in the inner lining of the esophagus (Esophagus_Mucosa) and in cultured fibroblasts (connective tissue cells grown in a laboratory), meaning modestly higher FAM120AOS gene activity in both tissue types. GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10761247?

rs10761247 is a common genetic variant located near the PHF2 gene. Large genetic studies have linked it to both income-related traits and body fat distribution in European-ancestry populations, though with small individual effect sizes.

Is rs10761247 linked to income or socioeconomic status?

Yes, this variant was identified as one of 162 loci associated with income in a study of 668,288 individuals of European descent. The polygenic index built from these loci explains only 1-5% of income variance, with roughly one-quarter of that from direct genetic effects.

Is rs10761247 linked to body fat or waist size?

This variant was identified among signals for waist-to-hip ratio adjusted for BMI in a meta-analysis of 694,649 individuals. Effects are generally stronger in women than in men, and the signal is one of hundreds identified in this large study.

What does rs10761247 do to PHF2 gene expression?

According to GTEx data, the alternative allele of rs10761247 is linked to modestly reduced PHF2 expression in two gastrointestinal tissues. The same variant also affects expression of three nearby genes (BARX1, ENSG00000289031, and FAM120AOS) in other tissues. These are mechanistic observations and do not directly predict health outcomes.

Do these findings apply to all populations?

Both studies were restricted primarily to individuals of European ancestry, so the findings cannot be assumed to apply equally to other populations. The income study also noted that heritability estimates for income vary with social and institutional conditions across regions and time.