rs11671664 (GIPR): BMI variant in East Asians

Key takeaways

• rs11671664 sits near the GIPR gene (chromosome 19q13, the GIPR/QPCTL locus) and is robustly associated with body mass index in East Asian populations at genome-wide significance
• This variant appears to mark an independent genetic signal from the GIPR variant (rs2287019) previously identified in European populations; the two share near-zero linkage disequilibrium in Asian samples
• Multiple large studies in East Asian populations, with combined samples exceeding 100,000 individuals, have replicated this association
• The alternate allele is linked to increased expression of GIPR in immune cells, suggesting a potential connection between incretin receptor signaling and immune function
• GIPR encodes the receptor for glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone that stimulates insulin release after meals and influences fat metabolism

What the research says rs11671664 at the GIPR/QPCTL locus on chromosome 19q13 reached genome-wide significance (P < 5×10^-8) for body mass index association in a three-stage meta-analysis combining approximately 83,000 East Asians across discovery and replication cohorts. The variant is not in linkage disequilibrium (LD - meaning it does not statistically co-occur) with rs2287019, the GIPR variant previously discovered in European-ancestry studies, with an r² of only 0.026 in Asians and weak LD of r²=0.264 even in Europeans; a conditional analysis placing both variants in the same statistical model confirmed that only rs11671664 retained significance in Asian samples, supporting it as an independent causal signal. The association was further confirmed across at least three additional independent East Asian GWAS and meta-analyses with combined sample sizes exceeding 100,000 individuals.

Reported associations

• Body mass index (BMI) - East Asian populations (primary discovery): rs11671664 was the lead SNP at this locus, reaching genome-wide significance (P < 5×10^-8) in a three-stage meta-analysis (stages I-III combined N ≈ 83,000 East Asians); conditional analysis confirmed it as a signal independent from the European-identified GIPR variant rs2287019
• Body mass index (BMI) - East Asian populations (independent replication): The GIPR locus at 19q13 satisfied the genome-wide significance threshold in a separate GWAS and replication study across 62,245 East Asian subjects
• Body mass index (BMI) - East Asian populations (meta-analytic replication): The GIPR/QPCTL locus was confirmed among genome-wide-significant BMI loci in a further meta-analysis of approximately 86,757 East Asians plus additional replication cohorts
• Body mass index (BMI) - Japanese population: The GIPR locus was among 85 obesity-associated loci reaching genome-wide significance in a Japanese GWAS (n = 173,430); this study also identified a genetic correlation between BMI and lymphocyte count (r = 0.18, P = 6.46×10^-¹^5) and enrichment of BMI-associated variants in CD19+ B lymphocytes, providing indirect support for a metabolic-immune link at this locus

Evidence quality The BMI association at this locus has been independently replicated across at least four large-scale East Asian studies with combined sample sizes well exceeding 100,000 participants, all achieving the genome-wide significance threshold of P < 5×10^-8. The primary discovery was conducted in a three-stage multi-ethnic design (total N ≈ 83,000 East Asians for stages I-III combined), with separate independent confirmation in a 62,245-person East Asian GWAS and two additional large meta-analyses. No conflicting findings were reported across the provided studies. A notable methodological strength is the conditional analysis demonstrating statistical independence of rs11671664 from the previously reported European GIPR variant, though the functional causal variant underlying either signal has not been identified in the provided data. Specific beta coefficients for BMI at rs11671664 are not reported in the available studies; the discovery meta-analysis notes that typical BMI-associated SNPs explain greater than 3% of the BMI standard deviation, but this figure was not confirmed specifically for rs11671664. Evidence for this association in non-Asian populations is not reported in the provided studies.

Tissue-specific expression effects

• GIPR: The alternate allele is associated with increased GIPR expression in EBV-transformed lymphocytes (a widely used B-cell model), a finding that may connect incretin receptor activity in immune cells to the metabolic phenotype GTEx Portal
• EML2-AS1: A long non-coding RNA near the locus shows increased expression across multiple tissues with the alternate allele, including EBV-transformed lymphocytes, cultured fibroblasts, pancreas, lung, and whole blood GTEx Portal
• DMWD: The alternate allele is associated with reduced DMWD expression in brain cerebellum GTEx Portal
• SYMPK: The alternate allele is associated with reduced SYMPK expression in tibial artery GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.