TY - JOUR
T1 - Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: The FAMOS study
AU - Ralston, Stuart H.
AU - Galwey, Nick
AU - Mackay, Ian
AU - Albagha, Omar M.E.
AU - Cardon, Lon
AU - Compston, Juliet E.
AU - Cooper, Cyrus
AU - Duncan, Emma
AU - Keen, Richard
AU - Langdahl, Bente
AU - McLellan, Alastair
AU - O'Riordan, Jeffrey
AU - Pols, Huibert A.
AU - Reid, David M.
AU - Uitterlinden, Andre G.
AU - Wass, John
AU - Bennett, Simon T.
N1 - © The Author 2005. Published by Oxford University Press. All rights reserved.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - 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 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.
AB - 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 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.
UR - http://www.mendeley.com/research/loci-regulation-bone-mineral-density-men-women-identified-genome-wide-linkage-scan-famos-study
U2 - 10.1093/hmg/ddi088
DO - 10.1093/hmg/ddi088
M3 - Article
SN - 0964-6906
VL - 14
SP - 943
EP - 951
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 7
ER -