rs11543260 (COQ10A): Kidney Function & Metabolism

Key takeaways

• rs11543260 is located near the COQ10A (coenzyme Q10 binding protein A) gene and has been identified in large-scale GWAS studies of kidney function and circulating metabolic traits
• GTEx data show this variant's alternate allele reduces COQ10A expression in the cerebellum, cerebellar hemisphere, and nucleus accumbens, as well as in lymphocytes
• The variant also increases ITGA7 expression in testis and RDH5 expression in lymphocytes and testis, and reduces NXPH4 expression in liver
• Evidence comes from discovery-scale studies spanning up to 1.5 million individuals; specific per-variant effect sizes for rs11543260 are not reported in the available excerpts

What the research says A genome-wide association study of kidney function in 1.5 million individuals identified 878 loci and used methylome data from 443 kidneys, transcriptome profiles from 686 samples, and single-cell open chromatin in 57,229 kidney cells to prioritize causal genes; this region was among the loci examined, with proximal tubule metabolism highlighted as a key pathway PMID 35551307. A trans-ancestral metabolomics GWAS of 249 circulating small-molecule and lipoprotein traits in approximately 450,000 UK Biobank participants across three ancestral groups identified 29,824 locus-metabolite associations at 753 genomic regions and assigned effector genes at over 100 loci through rare-to-common allelic series. A cross-population atlas of 220 phenotypes in up to 628,000 individuals (BioBank Japan, UK Biobank, FinnGen) identified approximately 5,000 new loci and used statistical decomposition to reveal latent genetic components underlying disease classifications PMID 34385711.

Reported associations

• Kidney function: This locus was among 878 regions in a 1.5-million-individual study; methylome, transcriptome, and single-cell chromatin data from kidney tissue were used to prioritize causal mechanisms, with proximal tubule metabolic pathways emphasized PMID 35551307
• Circulating metabolites and lipoproteins: The region appears among 753 loci associated with 249 NMR-measured metabolic traits in approximately 450,000 UK Biobank participants at a metabolome-adjusted threshold of P < 2.0 × 10^-¹^0; measured traits included lipoprotein subclasses, amino acids, and ketone bodies
• Multi-phenotype associations: The locus appears in a cross-population atlas of 220 phenotypes including disease diagnoses, biomarkers, and medication use, meta-analyzed across approximately 628,000 individuals PMID 34385711

Evidence quality All three source studies are large discovery-scale GWAS at genome-wide significance. The kidney function study PMID 35551307 is the largest (1.5 million individuals) and provides multi-stage mechanistic support - methylome from 443 kidneys, transcriptome from 686 samples, single-cell chromatin from 57,229 kidney cells - with 87% of loci having target genes prioritized. The metabolomics study used a stringent metabolome-adjusted threshold (P < 2.0 × 10^-¹^0) across three UK Biobank ancestral groups. The cross-population atlas PMID 34385711 adds multi-ancestry meta-analysis across approximately 628,000 participants. Per-variant statistics (p-values, odds ratios, beta coefficients) for rs11543260 are not reported in the available excerpts. GTEx eQTL analysis (v11, 953 donors, FDR < 0.05) provides independent molecular evidence linking this variant to gene expression changes across brain and immune tissues GTEx Portal.

Tissue-specific expression effects

• COQ10A: The alternate allele is associated with reduced expression in four tissues at GTEx FDR < 0.05 - brain cerebellum, brain cerebellar hemisphere, brain nucleus accumbens (basal ganglia), and EBV-transformed lymphocytes (a standardized B-cell line used in genomic research); the cerebellum and cerebellar hemisphere show the largest reductions GTEx Portal
• ITGA7 (integrin alpha-7): Increased expression in testis GTEx Portal
• RDH5 (retinol dehydrogenase 5): Increased expression in EBV-transformed lymphocytes and in testis GTEx Portal
• NXPH4 (neurexophilin-4): Reduced expression in liver GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.