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

Frauke Degenhardt, Petra Niklowitz, Silke Szymczak, Gunnar Jacobs, Wolfgang Lieb, Thomas Menke, Matthias Laudes, Tõnu Esko, Stephan Weidinger, Andre Franke, Frank Döring, Simone Onur

Journal: Human molecular genetics 2017;25(13):2881-2891

PMID: 27149984

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Abstract

Coenzyme Q (CoQ) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ 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 CoQ 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 , β = 0.063, CI [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 , β = -0.034, CI [-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 CoQ levels. In summary, this study demonstrates that serum CoQ levels are associated with common genetic loci that are linked to neuronal diseases.

Address: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany.; Children's Hospital Datteln, Witten/Herdecke University, Dr.-Friedrich-Steiner Str. 5, 45711 Datteln, Germany.; Institute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Niemannsweg 11, Haus 1, 24105 Kiel, Germany.; Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, Haus 6, 24105 Kiel, Germany.; Estonian Research Center, University of Tartu, Riia 23b, 51010, Tartu, Estland.; Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 7, 24105 Kiel, Germany.; Division of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany [email protected].; Division of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany.

DOI: 10.1093/hmg/ddw134

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MeSH Terms: Adult, Aged, Ataxia, Calcium-Binding Proteins, Cell Adhesion Molecules, Neuronal, Collectins, Cross-Sectional Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Mitochondrial Diseases, Muscle Weakness, Nerve Degeneration, Nerve Tissue Proteins, Neural Cell Adhesion Molecules, Neurons, Polymorphism, Single Nucleotide, Receptors, Scavenger, Ubiquinone