Genome-wide association study of serum coenzyme Q₁₀ levels identifies susceptibility loci linked to neuronal diseases

Coenzyme Q₁₀ (CoQ₁₀) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ₁₀ is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ₁₀ deficiencies show noticeable symptoms in tissues (e.g. kidney) and cell types (e.g. neurons) with a high energy demand. To identify common genetic variants influencing serum CoQ₁₀ levels, we performed a fixed effects meta-analysis in two independent cross-sectional Northern German cohorts comprising 1300 individuals in total. We identified two genome-wide significant susceptibility loci. The best associated single nucleotide polymorphism(SNP) was rs9952641 (P value =1.31 × 10^-8, β=0.063, CI_0.95 [0.041, 0.085]) within the COLEC12 gene on chromosome 18. The SNP rs933585 within the NRXN-1 gene on chromosome 2 also showed genome wide significance (P value =3.64 × 10^-8, β=-0.034, CI_0.95 [-0.046, -0.022]). Both genes have been previously linked to neuronal diseases like Alzheimer's disease, autism and schizophrenia. Among our 'top-10' associated variants, four additional loci with known neuronal connections showed suggestive associations with CoQ₁₀ levels. In summary, this study demonstrates that serum CoQ₁₀ levels are associated with common genetic loci that are linked to neuronal diseases.