rs10953541 (BCAP29): Basal Ganglia Brain Expression

Key takeaways

• rs10953541 sits in a chromosomal region shared by DUS4L and BCAP29 (B-cell receptor-associated protein 29), influencing the activity of at least four genes across multiple tissues
• GTEx data from 953 donors links the alternate allele to increased BCAP29 expression in five brain regions, strongest in the caudate and putamen - basal ganglia structures involved in movement and decision-making
• The alternate allele is also linked to reduced SLC26A4 expression in the pituitary gland and increased HBP1 and COG5 expression in testis and caudate, respectively
• Large-scale genetic studies of blood and urine biomarkers (n=363,228) and coronary artery disease have examined variants at this locus; specific associations and effect sizes for rs10953541 are not detailed in the available study text

What the research says A genome-wide association study of 35 blood and urine biomarkers in 363,228 UK Biobank participants identified 1,857 genomic loci associated with at least one laboratory measurement, with this region among those systematically analyzed PMID 33462484. A coronary artery disease (CAD) meta-analysis in Europeans and South Asians, including approximately 15,420 cases and 15,062 controls in discovery and 21,408 cases and 19,185 controls in replication across roughly 575,000 genotyped SNPs, also queried variants at this locus PMID 21378988. GTEx v11 eQTL (expression quantitative trait locus - a variant that affects how much of a gene is produced) analysis using 953 donors identifies rs10953541 as influencing BCAP29 expression across five brain regions, with p-values as low as 5.6e-12 in the caudate GTEx Portal.

Reported associations

• Blood and urine biomarkers: The locus was analyzed in a GWAS of 35 laboratory measurements in 363,228 UK Biobank participants; the study identified over 1,800 total biomarker-associated loci, but the specific measurement(s) linked to rs10953541 are not described in the available study abstract PMID 33462484
• Coronary artery disease (context): A European and South Asian CAD meta-analysis queried variants at this locus as part of its genome-wide sweep; the five newly significant loci in that study were at other chromosomal locations, and no specific CAD effect for rs10953541 is reported PMID 21378988
• BCAP29 brain expression (eQTL): The alternate allele is associated with increased BCAP29 expression in the putamen (slope +0.32, p=1.5e-10), caudate (slope +0.29, p=5.6e-12), hypothalamus (slope +0.25, p=4.4e-10), cerebellar hemisphere (slope +0.20, p=5.6e-9), and anterior cingulate cortex (slope +0.17, p=1.4e-7) GTEx Portal
• COG5 brain expression (eQTL): The alternate allele is associated with increased COG5 expression in the caudate (slope +0.21, p=3.0e-7) GTEx Portal
• SLC26A4 pituitary expression (eQTL): The alternate allele is associated with reduced SLC26A4 expression in the pituitary gland (slope -0.30, p=2.9e-5) GTEx Portal
• HBP1 testis expression (eQTL): The alternate allele is associated with increased HBP1 expression in the testis (slope +0.20, p=3.3e-9) GTEx Portal

Evidence quality The UK Biobank biomarker GWAS is well-powered (n=363,228), applied a Bonferroni-corrected significance threshold (p < 5e-9 for imputed variants), and benchmarked results against 42 previously published cohorts for 25 of the 35 biomarkers, showing high consistency in effect sizes PMID 33462484. The CAD meta-analysis included robust two-stage replication across approximately 21,400 additional cases and 19,000 additional controls in a combined European and South Asian sample PMID 21378988. GTEx eQTL signals for BCAP29 are strongly supported across five independent brain regions (953 donors, FDR - false discovery rate - less than 0.05), with the caudate signal reaching p=5.6e-12 GTEx Portal. Key limitations: the available GWAS text does not specify which biomarker rs10953541 is associated with; the CAD evidence is indirect, with no top-level CAD association reported at this locus; and eQTL effects describe molecular regulation, not confirmed disease mechanisms.

Tissue-specific expression effects

• BCAP29: The alternate allele is linked to increased expression across five brain regions - putamen, caudate, hypothalamus, cerebellar hemisphere, and anterior cingulate cortex (involved in cognition and emotion regulation) - strongest in the basal ganglia (caudate and putamen) GTEx Portal
• COG5: The alternate allele is linked to increased expression in the caudate GTEx Portal
• SLC26A4: The alternate allele is linked to reduced expression in the pituitary gland GTEx Portal
• HBP1: The alternate allele is linked to increased expression in the testis GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.