Expressive

rs118016381 (PPL): Body Size and Composition Signal

Key takeaways

  • rs118016381 near the PPL gene is one of 106 newly reported genome-wide signals for body size traits in a study of up to 267,616 people
  • It was discovered using whole-genome sequencing combined with deep imputation across 12 measures of height, weight, and fat distribution
  • The alternate allele is linked to increased ZNF500 gene activity in fat tissue, lung, skin, and several other tissues
  • The alternate allele is also linked to increased SMIM22 activity in brain cerebellum regions
  • The study was limited to European-ancestry populations and did not report a specific effect size for this variant

Key takeaways

  • rs118016381, located near the PPL gene, is one of 106 previously unreported genome-wide significant signals for body size and composition traits identified in a study of up to 267,616 individuals
  • The signal was discovered through a hybrid whole-genome sequencing and deep imputation approach covering 15,844,966 variants across 12 anthropometric measures including BMI, height, waist circumference, and fat mass
  • The alternate allele at this variant is linked to increased ZNF500 gene activity across several tissues including subcutaneous adipose tissue, lung, and skin
  • The alternate allele is also linked to increased SMIM22 gene activity in cerebellar brain regions
  • Evidence is from a single large European-ancestry study and does not include a per-variant effect size for this specific signal

What the research says A hybrid whole-genome sequencing and imputation study covering 15,844,966 sequence variants examined 12 anthropometric traits - including BMI, height, waist circumference, hip circumference, waist-to-hip ratio, total fat mass, total lean mass, and trunk fat mass - and identified rs118016381, near the PPL locus, as one of 106 previously unreported genome-wide significant signals for body size and composition. The discovery stage included 57,129 individuals and the follow-up stage added 210,823 participants, for a combined total of up to 267,616 people of European descent. Fine mapping resolved 23 of the 106 novel signals to one or two likely causal variants, and signal enrichment was noted in cis expression QTLs in relevant tissues, consistent with the eQTL activity observed at this locus.

Reported associations

  • Anthropometric traits (body size and composition): rs118016381 near the PPL locus was identified as a genome-wide significant signal for one or more of 12 body size and composition measures in up to 267,616 individuals of European descent; traits examined included BMI, weight, height, waist circumference, hip circumference, waist-to-hip ratio, total fat mass, total lean mass, and trunk fat mass

Evidence quality The association was identified in a large multi-stage study: a discovery set of 57,129 individuals followed by replication in 210,823 participants, reaching a combined total of up to 267,616 people of European descent. The study focused exclusively on European-ancestry populations, which limits how broadly findings apply across other ancestry groups. The provided text does not report a specific per-variant effect size (such as an odds ratio, beta coefficient, or percentage of variance explained) for rs118016381 individually. It is one of 106 novel signals; 23 of these were resolved by fine mapping to one or two likely causal variants, but whether this specific signal is among those fine-mapped signals is not stated. No conflicting findings were reported within the single study provided. The evidence should be considered preliminary pending independent replication in diverse populations.

Tissue-specific expression effects

  • ZNF500: the alternate allele is associated with increased expression in subcutaneous adipose tissue, lung, tibial nerve, skin (sun-exposed lower leg), EBV-transformed lymphocytes, and cultured fibroblasts GTEx Portal
  • SMIM22: the alternate allele is associated with increased expression in cerebellum and cerebellar hemisphere brain regions GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs118016381 and what gene is it near?

rs118016381 is a genetic variant located near the PPL gene (Periplakin). It was identified in a large genome-wide study as a signal associated with body size and fat distribution traits in up to 267,616 people.

What body traits is rs118016381 linked to?

The variant was identified as a genome-wide significant signal in a study measuring 12 anthropometric traits, including BMI, height, waist circumference, hip circumference, waist-to-hip ratio, total fat mass, total lean mass, and trunk fat mass. The available text does not specify which single trait shows the strongest association.

How large was the study that identified rs118016381?

The study combined whole-genome sequencing and imputation data from up to 267,616 individuals of European descent, with a discovery stage of 57,129 people and a follow-up stage of 210,823 additional participants.

Does rs118016381 affect gene expression in any tissues?

GTEx data show the alternate allele is associated with increased ZNF500 expression in subcutaneous fat, lung, skin, tibial nerve, lymphocytes, and fibroblasts. It is also associated with increased SMIM22 expression in cerebellar brain regions.

How strong is the evidence for rs118016381?

The signal reached genome-wide significance in a large study of up to 267,616 people, which is a high statistical bar. However, data come from a single study focused on European-ancestry populations, and a specific effect size for this variant was not reported in the available text, so the evidence should be considered preliminary.