rs10910078 (PLCH2): BMI-associated genetic locus

Key takeaways

• rs10910078 is located near PLCH2 (Phospholipase C eta 2), a gene involved in intracellular calcium signaling, and has been identified as one of over 900 genome-wide significant loci for body mass index (BMI).
• The association was found in a large meta-analysis combining data from the Million Veteran Program, UK Biobank, and other cohorts, with European ancestry sample sizes of approximately 1.1 million participants and roughly 100,000 African ancestry participants.
• A genetic risk score built from 2,446 BMI-associated variants was linked to 316 medical diagnoses in the Million Veteran Program, with 96.5% of those diagnoses showing increased risk with higher genetically predicted BMI.
• Mendelian randomization in the same study confirmed BMI's contribution to heart failure, ischemic heart disease, atrial fibrillation, chronic kidney disease, respiratory failure, asthma, and musculoskeletal and skin conditions.
• The per-allele effect size for rs10910078 specifically is not reported in the available study text.

What the research says rs10910078 is located near PLCH2, a gene whose protein product participates in intracellular calcium signaling. It was identified among 906 genome-wide significant loci for BMI in a large meta-analysis combining the Million Veteran Program with UK Biobank and other cohorts, encompassing approximately 1.1 million European ancestry participants and roughly 100,000 African ancestry participants. A BMI genetic risk score built from 2,446 associated variants was linked to 316 distinct diagnoses in the Million Veteran Program electronic health records, with 96.5% of those diagnoses showing increased risk with higher genetically predicted BMI.

Reported associations

• Body mass index: Identified as one of 906 genome-wide significant loci in European ancestry populations (N~1.1 million); 41 significant loci were also found in African ancestry populations (N~100,000). The per-allele effect size for rs10910078 alone is not reported in the available study text.
• Broad disease risk via BMI genetic risk score: A 2,446-variant score was associated with 316 diagnoses in the Million Veteran Program, with 96.5% of those diagnoses showing increased risk with higher genetically predicted BMI.
• Cardiovascular disease: Mendelian randomization confirmed that genetically predicted higher BMI is associated with heart failure, ischemic heart disease, and atrial fibrillation.
• Chronic kidney disease: Mendelian randomization confirmed an association between genetically predicted higher BMI and chronic renal failure.
• Respiratory conditions: Mendelian randomization confirmed associations for respiratory failure and asthma.
• Musculoskeletal and skin conditions: Mendelian randomization confirmed associations spanning musculoskeletal and dermatologic systems.

Evidence quality The BMI association for this locus comes from one of the largest GWAS meta-analyses conducted for this trait, with European ancestry sample sizes of approximately 1.1 million and African ancestry sample sizes of approximately 100,000 participants. Of the 906 European ancestry loci, 364 (roughly 40%) were reported as novel findings; among the 41 African ancestry loci, 6 were novel. This raises the possibility that rs10910078 may be among the newly identified signals that require independent replication before the association is considered firmly established. Critically, the disease associations described above are derived from a 2,446-variant BMI score as a whole, not from this single variant in isolation; the specific contribution of rs10910078 to any of those disease risks cannot be determined from the available text. No p-value, odds ratio, or per-allele beta coefficient for this variant specifically is provided in the available study excerpt, and its evidence should be considered preliminary pending replication.

Lifestyle considerations No lifestyle considerations on file for this variant.