title: Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study.
abstract: Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and an increased risk of fracture. Bone mineral density (BMD) is a highly heritable trait and a key determinant of osteoporotic fracture risk, but the genes responsible are incompletely defined. Here, we identified quantitative trait loci (QTL) for regulation of BMD by a genome wide scan involving 3691 individuals from 715 families, who were selected because of reduced BMD values at the lumbar spine (LS-BMD) or femoral neck (FN-BMD) in probands. Linkage analysis was conducted in the study group as a whole with correction for age, gender, weight and height. Further analyses were conducted for men and women separately to identify gender-specific QTL and for those under and over the age of 50 years to distinguish QTL for peak bone mass from those that influence bone mass in older people. No regions of suggestive or significant linkage were identified when data from all subjects were analyzed together. On subgroup analysis, however, we identified a significant QTL for FN-BMD on chromosome 10q21 (LOD score +4.42; men < or =50 years) and two suggestive QTL for LS-BMD on chromosomes 18p11 (LOD score +2.83; women >50 years) and 20q13 (LOD score +3.20; women < or =50 years). We identified five other QTL for BMD with LOD scores of greater than +2.20 on chromosomes 3q25, 4q25, 7p14, 16p13 and 16q23. This study provides evidence for gender-specific, site-specific and age-specific QTL, which regulate BMD in humans, and illustrates the importance of conducting subgroup analysis to detect these loci.
authors.affiliation: Rheumatic Diseases Unit, University of Edinburgh Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK. stuart.ralston@ed.ac.uk
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Nick
authors.initials: N
authors.lastname: Galwey
authors.forename: Ian
authors.initials: I
authors.lastname: MacKay
authors.forename: Omar M E
authors.initials: OM
authors.lastname: Albagha
authors.forename: Lon
authors.initials: L
authors.lastname: Cardon
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Compston
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Emma
authors.initials: E
authors.lastname: Duncan
authors.forename: Richard
authors.initials: R
authors.lastname: Keen
authors.forename: Bente
authors.initials: B
authors.lastname: Langdahl
authors.forename: Alastair
authors.initials: A
authors.lastname: McLellan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: O'Riordan
authors.forename: Huibert A
authors.initials: HA
authors.lastname: Pols
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: John
authors.initials: J
authors.lastname: Wass
authors.forename: Simon T
authors.initials: ST
authors.lastname: Bennett
mesh_terms: D015519:Bone Density; D005260:Female; D005272:Femur Neck / Q000473:pathology; D008040:Genetic Linkage; D016678:Genome; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D010024:Osteoporosis / Q000235:genetics*; D040641:Quantitative Trait Loci; D017422:Sequence Analysis, DNA; D012737:Sex Factors