title: Genome-wide association study of serum coenzyme Q10 levels identifies susceptibility loci linked to neuronal diseases.
abstract: Coenzyme Q10(CoQ10) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ10is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ10deficiencies 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 CoQ10levels, 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, CI0.95[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, CI0.95[-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 CoQ10levels. In summary, this study demonstrates that serum CoQ10levels are associated with common genetic loci that are linked to neuronal diseases.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Degenhardt
authors.affiliation: Children's Hospital Datteln, Witten/Herdecke University, Dr.-Friedrich-Steiner Str. 5, 45711 Datteln, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Niklowitz
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.affiliation: Institute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Niemannsweg 11, Haus 1, 24105 Kiel, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobs
authors.affiliation: Institute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Niemannsweg 11, Haus 1, 24105 Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Children's Hospital Datteln, Witten/Herdecke University, Dr.-Friedrich-Steiner Str. 5, 45711 Datteln, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Menke
authors.affiliation: Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, Haus 6, 24105 Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Laudes
authors.affiliation: Estonian Research Center, University of Tartu, Riia 23b, 51010, Tartu, Estland.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 7, 24105 Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Division of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany sek@molprev.uni-kiel.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
authors.affiliation: Division of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Onur
mesh_terms: D000328:Adult; D000368:Aged; D001259:Ataxia / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D037222:Collectins / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D009474:Neurons; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051116:Receptors, Scavenger / Q000235:genetics; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: C422442:COLEC12 protein, human; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D037222:Collectins; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D051116:Receptors, Scavenger; D014451:Ubiquinone; C024989:coenzyme Q10