title: Heritability of bone mineral density in a multivariate family-based study.
abstract: There is evidence for a genetic contribution to bone mineral density (BMD×). Different loci affecting BMD have been identified by diverse linkage and genome-wide association studies. We studied the heritability of and the correlations among six densitometric phenotypes and four bone mass/fracture phenotypes. For this purpose, we used a family-based study of the genetics of osteoporosis, the Genetic Analysis of Osteoporosis Project. The primary aim of our study was to examine the roles of genetic and environmental factors in determining osteoporosis-related phenotypes. The project consisted of 11 extended families from Spain. All of them were selected through a proband with osteoporosis. BMD was measured using dual-energy X-ray absorptiometry. The proportion of variance of BMD attributable to significant covariates ranged from 25% (for femoral neck BMD) to 48% (for whole-body total BMD). The vast majority of the densitometric phenotypes had highly significant heritability, ranging from 0.252 (whole-body total BMD) to 0.537 (trochanteric BMD) after correcting for covariate effects. All of the densitometric phenotypes showed high and significant genetic correlations (from -0.772 to -1.000) with a low bone mass/osteopenia condition (Affected 3). Our findings provide additional evidence on the heritability of BMD and a strong genetic correlation between BMD and bone mass/fracture phenotypes in a Spanish population. Our results emphasize the importance of detecting genetic risk factors and the benefit of early diagnosis and especially therapeutic and preventive strategies.
authors.affiliation: Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain, nhernandezd@santpau.cat.
authors.forename: Nerea
authors.initials: N
authors.lastname: Hernandez-de Sosa
authors.forename: Georgios
authors.initials: G
authors.lastname: Athanasiadis
authors.forename: Jorge
authors.initials: J
authors.lastname: Malouf
authors.forename: Ana
authors.initials: A
authors.lastname: Laiz
authors.forename: Ana
authors.initials: A
authors.lastname: Marin
authors.forename: Silvia
authors.initials: S
authors.lastname: Herrera
authors.forename: Jordi
authors.initials: J
authors.lastname: Farrerons
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Soria
authors.forename: Jordi
authors.initials: J
authors.lastname: Casademont
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013030:Spain; D055815:Young Adult