title: Genome-wide linkage scan for quantitative trait loci underlying normal variation in heel bone ultrasound measures.
abstract: Quantitative ultrasound (QUS) traits are correlated with bone mineral density (BMD), but predict risk for future fracture independent of BMD. Only a few studies, however, have sought to identify specific genes influencing calcaneal QUS measures. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing normal variation in QUS traits. QUS measures were collected from a total of 719 individuals (336 males and 383 females) from the Fels Longitudinal Study who have been genotyped and have at least one set of QUS measurements. Participants ranged in age from 18.0 to 96.6 years and were distributed across 110 nuclear and extended families. Using the Sahara ® bone sonometer, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI) were collected from the right heel. Variance components based linkage analysis was performed on the three traits using 400 polymorphic short tandem repeat (STR) markers spaced approximately 10 cM apart across the autosomes to identify QTL influencing the QUS traits. Age, sex, and other significant covariates were simultaneously adjusted. Heritability estimates (h²) for the QUS traits ranged from 0.42 to 0.57. Significant evidence for a QTL influencing BUA was found on chromosome 11p15 near marker D11S902 (LOD = 3.11). Our results provide additional evidence for a QTL on chromosome 11p that harbors a potential candidate gene(s) related to BUA and bone metabolism.
authors.affiliation: Lifespan Health Research Center, Wright State University, Boonshoft School of Medicine, Dayton, OH 45420, USA. miryoung.lee@wright.edu
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: A C
authors.initials: AC
authors.lastname: Choh
authors.forename: K D
authors.initials: KD
authors.lastname: Williams
authors.forename: V
authors.initials: V
authors.lastname: Schroeder
authors.forename: T D
authors.initials: TD
authors.lastname: Dyer
authors.forename: J
authors.initials: J
authors.lastname: Blangero
authors.forename: S A
authors.initials: SA
authors.lastname: Cole
authors.forename: Wm C
authors.initials: WC
authors.lastname: Chumlea
authors.forename: D L
authors.initials: DL
authors.lastname: Duren
authors.forename: R J
authors.initials: RJ
authors.lastname: Sherwood
authors.forename: R M
authors.initials: RM
authors.lastname: Siervogel
authors.forename: B
authors.initials: B
authors.lastname: Towne
authors.forename: S A
authors.initials: SA
authors.lastname: Czerwinski
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000235:genetics*; D002111:Calcaneus / Q000000981:diagnostic imaging*; D002880:Chromosomes, Human, Pair 11; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D014644:Genetic Variation; D016678:Genome; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D012016:Reference Values; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D005819:Genetic Markers