title: Exploring correlation between bone metabolism markers and densitometric traits in extended families from Spain.
abstract: Osteoporosis is a common multifactorial disorder characterized by low bone mass and reduced bone strength that may cause fragility fractures. In recent years, there have been substantial advancements in the biochemical monitoring of bone metabolism through the measurement of bone turnover markers. Currently, good knowledge of the genetics of such markers has become an indispensable part of osteoporosis research. In this study, we used the Genetic Analysis of Osteoporosis Project to study the genetics of the plasma levels of 12 markers related to bone metabolism and osteoporosis. Plasma phenotypes were determined through biochemical assays and log-transformed values were used together with a set of covariates to model genetic and environmental contributions to phenotypic variation, thus estimating the heritability of each trait. In addition, we studied correlations between the 12 markers and a wide variety of previously described densitometric traits. All of the 12 bone metabolism markers showed significant heritability, ranging from 0.194 for osteocalcin to 0.516 for sclerostin after correcting for covariate effects. Strong genetic correlations were observed between osteocalcin and several bone mineral densitometric traits, a finding with potentially useful diagnostic applications. In addition, suggestive genetic correlations with densitometric traits were observed for leptin and sclerostin. Overall, the few strong and several suggestive genetic correlations point out the existence of a complex underlying genetic architecture for bone metabolism plasma phenotypes and provide a strong motivation for pursuing novel whole-genome gene-mapping strategies.
authors.affiliation: Unit of Genomics of Complex Diseases, Institute of Biomedical Research, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: athanasiadis@birc.au.dk.
authors.forename: Georgios
authors.initials: G
authors.lastname: Athanasiadis
authors.affiliation: Unit of Genomics of Complex Diseases, Institute of Biomedical Research, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Arranz
authors.affiliation: Unit of Genomics of Complex Diseases, Institute of Biomedical Research, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Andrey
authors.initials: A
authors.lastname: Ziyatdinov
authors.affiliation: Unit of Genomics of Complex Diseases, Institute of Biomedical Research, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Brunel
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Camacho
authors.affiliation: Departament of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Malouf
authors.affiliation: Departament of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Nerea Hernandez-de
authors.initials: NH
authors.lastname: Sosa
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Vila
authors.affiliation: Departament of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Casademont
authors.affiliation: Unit of Genomics of Complex Diseases, Institute of Biomedical Research, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Soria
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003720:Densitometry; D005190:Family; D005260:Female; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D013030:Spain; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Bone metabolism; Densitometry; Leptin; Osteocalcin; Osteoporosis