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

被引:15
作者
Degenhardt, Frauke [1 ]
Niklowitz, Petra [2 ]
Szymczak, Silke [1 ]
Jacobs, Gunnar [3 ,4 ]
Lieb, Wolfgang [3 ,4 ]
Menke, Thomas [2 ]
Laudes, Matthias [5 ]
Esko, Tonu [6 ]
Weidinger, Stephan [7 ]
Franke, Andre [1 ]
Doering, Frank [8 ]
Onur, Simone [8 ]
机构
[1] Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Schittenhelmstr 12, D-24105 Kiel, Germany
[2] Univ Witten Herdecke, Childrens Hosp Datteln, Dr Friedrich Steiner Str 5, D-45711 Datteln, Germany
[3] Christian Albrechts Univ Kiel, Inst Epidemiol, Niemannsweg 11,Haus 1, D-24105 Kiel, Germany
[4] Christian Albrechts Univ Kiel, Biobank PopGen, Niemannsweg 11,Haus 1, D-24105 Kiel, Germany
[5] Univ Hosp Schleswig Holstein, Dept Internal Med, Campus Kiel,Arnold Heller Str 3,Haus 6, D-24105 Kiel, Germany
[6] Univ Tartu, Estonian Res Ctr, Riia 23b, EE-51010 Tartu, Estonia
[7] Univ Hosp Schleswig Holstein, Dept Dermatol, Campus Kiel,Schittenhelmstr 7, D-24105 Kiel, Germany
[8] Christian Albrechts Univ Kiel, Inst Human Nutr & Food Sci, Div Mol Prevent, Heinrich Hecht Pl 10, D-24118 Kiel, Germany
关键词
MATRIX METALLOPROTEINASE-26; GENOTYPE IMPUTATION; SCAVENGER RECEPTOR; TNF-ALPHA; EXPRESSION; GENE; DEFICIENCY; UBIQUINONE; MUTATIONS; SCHIZOPHRENIA;
D O I
10.1093/hmg/ddw134
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Coenzyme Q(10) (CoQ(10)) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ(10) is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ(10) 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(10) 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 x 10(-8), beta = 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 x 10(-8), beta = -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 CoQ(10) levels. In summary, this study demonstrates that serum CoQ(10) levels are associated with common genetic loci that are linked to neuronal diseases.
引用
收藏
页码:2881 / 2891
页数:11
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