rs1147199 (SLC28A3/NTRK2): BMI neural pathway variant

Key takeaways

• rs1147199 at the SLC28A3 and NTRK2 locus has been linked to body mass index in East Asian studies of 173,430 Japanese and 153,950 Korean individuals
• BMI-associated genetic variants are enriched in neural tissue, consistent with the neural biology of this genomic region
• A multivariate study of nearly 5 million people found metabolic syndrome loci are enriched in brain tissue, converging with this locus
• Evidence is strongest in East Asian populations; cross-ancestry replication is ongoing
• No lifestyle-specific interactions for this variant are currently established

What the research says A genome-wide association study (GWAS, a method that scans the full genome for trait-linked variants) of body mass index (BMI, weight in kilograms divided by height in meters squared) in 173,430 Japanese individuals identified 112 novel BMI loci, combining 51 new findings from the Japanese cohort with 61 more from trans-ancestral meta-analysis integrating European data, all reaching genome-wide significance at P < 5.0 x 10^-8. A Korean cohort of 153,950 participants tested across 36 quantitative traits identified 301 previously unreported loci in the primary analysis, expanding to 4,588 loci through meta-analysis with the Korean Genome and Epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank. Multivariate genomic modeling of 18 adiposity and anthropometric measures found that the latent genetic factor specific to adiposity is enriched in neural tissue and pathways, while the factor for adipose distribution is enriched more broadly across physiological systems.

Reported associations

• Body mass index (Japanese cohort, n=173,430): Among 112 novel loci reaching genome-wide significance (P < 5.0 x 10^-8), confirmed through trans-ancestral meta-analysis with European data; BMI-associated variants in this study showed enrichment in CD19 immune cells and a genetic correlation of r=0.18 with lymphocyte count
• Body mass index and anthropometric traits (Korean cohort, n=153,950): Among 301 previously unreported loci across 36 quantitative traits, with SNP-based heritability across the studied traits ranging from 0.034 (alcohol intake) to 0.347 (height); meta-analysis across five biobanks extended discovery to 4,588 loci
• Adiposity latent factor: Genomic structural equation modeling of 18 anthropometric measures identified a latent adiposity factor whose genetic architecture is enriched specifically in neural tissue and pathways, distinct from the adipose distribution factor which is enriched more broadly
• Metabolic syndrome (n approximately 4.9 million): Among 1,307 loci associated with a composite phenotype including central obesity, elevated blood lipids (dyslipidemia), high blood pressure, and impaired blood sugar regulation (hyperglycemia), with enrichment in brain tissue; 11 genes were identified as strongly associated with this composite trait

Evidence quality The primary discovery evidence comes from two large East Asian cohorts both reaching genome-wide significance: a Japanese BMI study (n=173,430, P < 5.0 x 10^-8) and a Korean multi-trait study (n=153,950). Trans-ancestral meta-analysis incorporating European data (UK Biobank and others) supports broader generalizability, though the Korean cohort authors note that over 90% of historical GWAS participants are of European ancestry, meaning these East Asian findings address a critical representation gap and variant-level cross-ancestry replication is still being established. The metabolic syndrome multivariate analysis (n approximately 4.9 million) provides the greatest statistical power but covers a broader composite phenotype rather than BMI alone. Specific effect sizes such as beta coefficients or odds ratios for rs1147199 at this locus are not reported in the provided study excerpts. No explicit conflicting findings across the four contributing studies are identified; the neural tissue enrichment finding for BMI genetics is reported consistently across both the adiposity genomic SEM study and the metabolic syndrome GWAS.

Lifestyle considerations No lifestyle considerations on file for this variant.