title: Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase.
abstract: Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes.
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Ragnar P
authors.initials: RP
authors.lastname: Kristjansson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Asmundur
authors.initials: A
authors.lastname: Oddsson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Helgason
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gardar
authors.initials: G
authors.lastname: Sveinbjornsson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gudny A
authors.initials: GA
authors.lastname: Arnadottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Brynjar O
authors.initials: BO
authors.lastname: Jensson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Aslaug
authors.initials: A
authors.lastname: Jonasdottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Adalbjorg
authors.initials: A
authors.lastname: Jonasdottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: G
authors.initials: G
authors.lastname: Bragi Walters
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gerald
authors.initials: G
authors.lastname: Sulem
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Arna
authors.initials: A
authors.lastname: Oskarsdottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Benonisdottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Olafur B
authors.initials: OB
authors.lastname: Davidsson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Olafur Th
authors.initials: OT
authors.lastname: Magnusson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Department of Internal Medicine, Landspitali The National University Hospital of Iceland, 101 Reykjavik, Iceland.
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.affiliation: Department of Clinical Biochemistry, Akureyri Hospital, 600 Akureyri, Iceland.
authors.forename: Olof
authors.initials: O
authors.lastname: Sigurdardottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Ingileif
authors.initials: I
authors.lastname: Jonsdottir
authors.affiliation: Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), 109 Reykjavik, Iceland.
authors.forename: Gudmundur I
authors.initials: GI
authors.lastname: Eyjolfsson
authors.affiliation: Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland.
authors.forename: Isleifur
authors.initials: I
authors.lastname: Olafsson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.affiliation: deCODE genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000075368:Anoctamins; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D003402:Creatine Kinase / Q000097:blood*; D052283:Creatine Kinase, MM Form / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007055:Iceland; D007527:Isoenzymes / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000097:blood* / Q000235:genetics; D000080864:Lactate Dehydrogenase 5; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000235:genetics; D051116:Receptors, Scavenger; D012044:Regression Analysis; D000098902:CD163 Antigen
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C417665:CD163L1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D018118:Chloride Channels; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; C527700:LILRB5 protein, human; D008562:Membrane Glycoproteins; C484438:NINJ1 protein, human; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D051116:Receptors, Scavenger; C449926:STAB1 protein, human; D017242:Complement Factor H; D016173:Macrophage Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form
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