rs11062386 (TEX52/ITFG2): Height and Blood Traits

Key takeaways

• This variant near TEX52 and ITFG2 appears in large genomic studies of height, blood cell measurements, and physical aging.
• In spleen and immune-adjacent tissues, the ALT allele is linked to reduced activity of the nearby RHNO1 gene.
• In brain regions including the caudate and anterior cingulate, the ALT allele reduces activity of multiple neighboring genes.
• The ALT allele increases gene activity in the adrenal gland while reducing it in skin and brain, showing tissue-specific effects.
• Physical and cognitive aging have distinct genetic drivers: bone mineral density for physical decline, Alzheimer's disease liability for cognitive decline.

What the research says A trans-ethnic meta-analysis covering 15 hematological traits (red blood cell, white blood cell, and platelet measures) in 746,667 participants across five global populations identified 5,552 genome-wide significant trait-variant associations, with fine-mapping credible sets 30% smaller under multi-ancestry analysis than European-only analysis, and 71 novel loci not present in European-only data. A genome-wide association study (GWAS) of height in 5.4 million individuals across diverse ancestries identified 12,111 independent common variants clustered in 7,209 non-overlapping genomic segments averaging around 90 kb, collectively accounting for approximately 40% of phenotypic height variance in out-of-sample prediction in European ancestry populations, and approximately 10-20% in other ancestries. Longitudinal genome-wide analyses of UK Biobank participants found that accelerated physical decline has a distinct and much lower heritability (approximately 3.15%) compared to baseline physical function (approximately 31.38%), with bone mineral density (standardized Mendelian Randomization effect -0.05) and telomere length as primary genetic mediators, while cognitive decline was primarily driven by Alzheimer's disease genetic liability (standardized MR effect 0.17).

Reported associations

• Height: The genomic region near TEX52 (Testis Expressed 52) and ITFG2 (Integrin Alpha FG-GAP Repeat Containing 2) falls within the landscape covered by a GWAS of 5.4 million individuals that identified 12,111 height-associated common variants explaining approximately 40% of height variance in European ancestry populations, with effect sizes broadly similar across ancestries.
• Hematological traits: Trans-ethnic blood-cell analyses in 746,667 participants from five global populations covered this region across 15 phenotypes including platelet, red blood cell, and white blood cell measurements; 85 of 88 testable novel associations were replicated in the Million Veteran Program cohort, with 83 confirmed at a false discovery rate below 5%.
• Physical function decline: Longitudinal GWAS in UK Biobank identified a distinct genetic component for accelerated physical decline with a heritability of approximately 3.15%, driven partly by bone mineral density (standardized Mendelian Randomization effect -0.05) and telomere length.
• Cognitive aging: Longitudinal genome-wide analyses found cognitive decline is primarily driven by Alzheimer's disease genetic liability (standardized MR effect 0.17) and is genetically distinct from physical aging, with negligible overlap between the two.

Evidence quality The source studies represent large to very large discovery samples: 5.4 million individuals for height, 746,667 for blood-cell traits, and a multi-wave UK Biobank longitudinal cohort for aging phenotypes. The blood-cell study replicated 85 of 88 testable novel associations in an independent cohort (Million Veteran Program), with 83 confirmed at false discovery rate below 5% and 44 meeting a Bonferroni-adjusted threshold. The height study's 12,111 identified SNPs approach the theoretical limit for common-variant heritability in European ancestry populations, but prediction accuracy falls substantially in non-European ancestries (approximately 10-20% vs. 40%), indicating that further multi-ancestry work is needed. The aging study acknowledged potential selective attrition bias, as longitudinal participants represent a healthier subset of an already health-selected sample; the authors caution that careful modelling is crucial for valid inference. Specific per-SNP p-values or effect sizes for rs11062386 are not reported in the provided study excerpts.

Tissue-specific expression effects

• TULP3: The ALT allele increases expression in adrenal gland tissue, but reduces it in sun-exposed lower-leg skin, brain caudate basal ganglia, and non-sun-exposed suprapubic skin GTEx Portal
• RHNO1: The ALT allele is associated with reduced expression in spleen, esophagus mucosa, and subcutaneous adipose tissue GTEx Portal
• ENSG00000278356: The ALT allele is associated with reduced expression specifically in brain anterior cingulate cortex (area BA24) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.