Expressive

rs117933277 (MEGF11): Body Mass Index Variant

Key takeaways

  • Identified in one of the largest genetic studies of body mass index ever conducted, involving over 1.1 million participants of European ancestry
  • Located near MEGF11 (Multiple EGF Like Domains 11), one of 906 statistically significant genetic locations for BMI found in the study
  • Also linked to increased expression of DIS3L, a separate nearby gene, in cultured fibroblast cells
  • The exact effect size of this variant on BMI is not reported separately in available materials
  • Evidence comes from a single large study; independent confirmation has not been reported in available materials

Key takeaways

  • Identified in one of the largest genetic studies of body mass index ever conducted, involving over 1.1 million participants of European ancestry
  • Located near MEGF11 (Multiple EGF Like Domains 11), one of 906 statistically significant genetic locations for BMI found in the study, 364 of which were previously unknown
  • Also linked to increased expression of a separate nearby gene, DIS3L, in cultured fibroblast cells
  • The exact effect size of this variant on BMI is not reported separately in the available study materials
  • The BMI link comes from a single large study; confirmation from independent studies has not been reported in the available materials

What the research says A large genome-wide association meta-analysis of body mass index - conducted across approximately 1.1 million participants of European ancestry and roughly 100,000 participants of African ancestry - identified 906 genome-wide significant loci for BMI, including 364 novel loci, with this locus among those implicated. A genetic risk score built from 2,446 BMI variants was then applied in a phenome-wide analysis and found associations with 316 diagnoses in the Million Veteran Program, with 96.5% of those diagnoses showing increased risk alongside higher BMI. GTEx v11 data (953 donors) independently show that the alternate allele of this variant is associated with increased expression of DIS3L in cultured fibroblasts GTEx Portal.

Reported associations

  • Body mass index (BMI): This variant was identified as one of 906 genome-wide significant loci for BMI in a multi-ancestry analysis of approximately 1.1 million European ancestry and 100,000 African ancestry participants
  • DIS3L gene expression in fibroblasts: The alternate allele is associated with increased DIS3L expression in cultured fibroblasts (positive eQTL slope, p=1.8e-4, GTEx v11, 953 donors) GTEx Portal

Evidence quality The BMI association evidence comes from one of the largest GWAS analyses published to date, covering approximately 1.1 million European ancestry and 100,000 African ancestry participants and identifying 906 genome-wide significant loci. The study materials provided do not report the specific effect size or confidence interval for this variant individually, so the magnitude of its BMI association cannot be quantified from available data. The eQTL signal for DIS3L in cultured fibroblasts (p=1.8e-4) comes from GTEx v11 with 953 donors and is tissue-specific, with no effects in other tissues reported in the provided GTEx data. No information on independent replication of the BMI association at this locus is available from the provided materials; the variant-level association should be considered preliminary.

Tissue-specific expression effects

  • DIS3L: The alternate allele is associated with increased expression in cultured fibroblasts; no effects in other tissues are reported in the available data GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • genetic BMI predisposition and weight strategies Moderate

    G allele at MEGF11 rs117933277 increases BMI predisposition; physician guidance may optimize management

Exercise

  • aerobic and resistance exercise Moderate

    Regular exercise counteracts genetic BMI predisposition from the G risk allele

    150 min/week moderate aerobic activity plus resistance training 2+ days/week

Screening

  • weight and BMI trends Moderate

    G risk allele is associated with increased body mass index in large-scale GWAS study

    Measure weight and calculate BMI quarterly

Frequently asked questions

What is the MEGF11 gene?

MEGF11 stands for Multiple EGF Like Domains 11. It is a gene that emerged from large-scale genetic research into body mass index. Its precise biological role in weight regulation is still under investigation.

Is rs117933277 linked to obesity or BMI?

This variant was identified as one of 906 statistically significant genetic locations for body mass index in a study of over 1.1 million people of European ancestry. The specific effect size for this variant on BMI is not available in the provided study materials.

What does it mean that this variant affects DIS3L gene expression?

GTEx data show that carrying the alternate allele is associated with slightly higher expression of DIS3L in cultured fibroblasts. DIS3L is an RNA-processing enzyme. This is a potential molecular mechanism, not a clinical outcome.

How large was the study that identified this variant?

The study analyzed approximately 1.1 million participants of European ancestry and around 100,000 participants of African ancestry, identifying 906 genome-wide significant loci for body mass index.

What conditions are associated with BMI genetics?

The same research found that a genetic score for BMI was associated with 316 diagnoses in a large veterans health database, including heart conditions, kidney disease, asthma, and musculoskeletal conditions, with 96.5% of those diagnoses showing increased risk alongside higher BMI.