Expressive

rs10838738 (MTCH2): BMI-Associated Genetic Variant

Key takeaways

  • rs10838738 near MTCH2 is one of six genetic variants tied to body mass index at genome-wide significance, confirmed across studies totaling over 91,000 people.
  • MTCH2 and co-identified BMI genes are expressed in the central nervous system, suggesting neuronal circuits play a role in common body weight variation.
  • The alternate allele is linked to reduced C1QTNF4 expression in liver, lung, skin, adipose tissue, and skeletal muscle.
  • All discovery and replication cohorts were of European ancestry, so findings may not apply equally to other populations.

Key takeaways

  • rs10838738 near MTCH2 is one of six genetic variants tied to body mass index at genome-wide significance, confirmed across studies totaling over 91,000 people.
  • MTCH2 and co-identified BMI genes are expressed in the central nervous system, suggesting neuronal circuits play a role in common body weight variation.
  • The alternate allele is linked to reduced C1QTNF4 expression in liver, lung, skin, adipose tissue, and skeletal muscle.
  • All discovery and replication cohorts were of European ancestry, so findings may not apply equally to other populations.

What the research says rs10838738 sits near MTCH2, which was identified as one of six previously unknown genome-wide significant loci for body mass index (BMI) in a meta-analysis of 15 genome-wide association studies (GWAS) covering more than 32,000 individuals of European ancestry, with the signal replicated in 14 additional cohorts totaling over 59,000 further individuals (combined n > 91,000) PMID 19079260. Several of the likely causal genes at the newly identified BMI loci, including those near MTCH2, are highly expressed or known to function in the central nervous system (CNS), pointing to neuronal pathways as contributors to body weight predisposition PMID 19079260.

Reported associations

  • Body mass index: The MTCH2 locus reached genome-wide significance (P < 5 x 10^-8) for BMI in a two-stage GWAS meta-analysis (stage 1: n > 32,000; stage 2 replication: n > 59,000; all European ancestry); a specific per-allele effect size for rs10838738 is not reported in the available study text PMID 19079260

Evidence quality The BMI association at this locus was established through a well-powered two-stage design: a discovery meta-analysis of 15 GWAS (n > 32,000) followed by replication in 14 independent cohorts (n > 59,000), with the association crossing the standard genome-wide significance threshold of P < 5 x 10^-8 PMID 19079260. All cohorts were of European ancestry, which limits generalizability across populations. The available study text does not provide a per-allele BMI effect size specific to rs10838738; the 0.2-0.4 kg/m2 per-allele figures cited in the same paper refer to FTO and MC4R, not to the six newly identified loci, and should not be assumed to apply here. No conflicting findings for this locus were identified in the provided studies.

Tissue-specific expression effects

  • C1QTNF4: The alternate allele of rs10838738 is associated with reduced expression of C1QTNF4 across a broad range of tissues, including spleen, EBV-transformed lymphocytes, liver, sun-exposed and non-sun-exposed skin, lung, subcutaneous adipose tissue, and skeletal muscle 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.

Diet

  • dietary fiber Low

    Adequate fiber intake supports digestive health and reduces straining, factors that mitigate hemorrhoid risk in genetically predisposed individuals

    maintain 25-35g dietary fiber daily from vegetables, fruits, whole grains, legumes

Discuss with your doctor

  • hemorrhoidal disease risk and prevention strategies Moderate

    rs10838738 A allele associated with increased hemorrhoidal disease risk (p=2e-9, OR=1.03 per allele in n=944,133)

    discuss genetic risk factors and prevention strategies with healthcare provider

Screening

  • weight and lipid levels Low

    rs10838738 A allele associated with increased BMI (0.07 kg/m2 per allele) and triglyceride levels in lipoprotein particles

    regular monitoring of weight, BMI, and lipid panel (especially triglycerides) every 1-2 years

Frequently asked questions

What does the MTCH2 gene do?

In genome-wide research, variants near MTCH2 have been linked to body mass index regulation. The gene is expressed in the central nervous system, suggesting it may influence body weight through neuronal pathways. Specific molecular functions of MTCH2 are not described in the available studies.

Is rs10838738 associated with obesity?

rs10838738 near MTCH2 reached genome-wide significance for body mass index in a meta-analysis of over 91,000 individuals. The study reporting this finding did not provide a per-allele effect size specific to this variant.

Which tissues does rs10838738 affect gene expression in?

According to GTEx data, the alternate allele of rs10838738 is associated with reduced expression of C1QTNF4 in spleen, lymphocytes, liver, skin, lung, subcutaneous adipose tissue, and skeletal muscle.

How was the BMI association for rs10838738 discovered?

The association was identified in two stages: a discovery meta-analysis of 15 GWAS covering more than 32,000 individuals, followed by replication in 14 independent cohorts covering more than 59,000 individuals, all of European ancestry.

Why does it matter that MTCH2 is expressed in the brain?

Rare mutations causing severe obesity are known to act through brain structures such as the hypothalamus. The finding that a common BMI locus like MTCH2 is also expressed in the CNS suggests that neuronal body weight regulation may contribute to typical weight variation in the general population, not only extreme obesity cases.