CONTEXT: Bone mass is under strong genetic control, with heritability estimates greater than 50% and is likely determined by complex interactions between genetic and environmental factors. OBJECTIVE: The objective of the study was to localize genes contributing to bone mineral density (BMD) variation. DESIGN: An autosomal genome-wide scan for BMD at the lumbar spine and femoral neck was conducted with variance components linkage methods. PARTICIPANTS: A total of 103 pedigrees (Network in Europe on Male Osteoporosis Family Study) ascertained through a male relative with low (Z-score < or = -2) BMD values at either lumbar spine or femoral neck. MAIN OUTCOME MEASURES: Nonparametric multipoint logarithm of the odds ratio scores for lumbar spine and femoral neck BMD values adjusted for age, gender, and body mass index. RESULTS: We identified a total of eight chromosomal regions with logarithm of the odds ratio score of 1.5 or greater (P < or = 5 x 10(-3)): on 1q42-43, 11q12-13, 12q23-24, 17q21-23, 21q22, and 22q11 for lumbar spine and on 5q31-33 and 13q12-14 for femoral neck BMD. CONCLUSIONS: Four of our detected quantitative trait loci (QTL) reached the genome-wide criteria for significant (17q,21-23, P < or = 2 x 10(-5)) or suggestive (11q12-13, 22q11, and 13q12-14, P < or = 7 x 10(-4)) linkage. Apart from 22q11, which is a novel QTL, all other loci provide consistent replication for previously reported QTLs for BMD and other bone-related traits. Finally, several of our specific-linkage areas encompass prominent candidate genes: type 1 collagen (COL1A1) and the sclerosteosis/van Buchem disease (SOST) genes on 17q21-23; the low-density lipoprotein receptor-related protein 5 (LRP5) gene on 11q12-13; and the rank ligand gene on 13q12-14. Further analysis of these positive regions by fine linkage disequilibrium mapping is thus warranted.
CONTEXT: Bone mass is under strong genetic control, with heritability estimates greater than 50% and is likely determined by complex interactions between genetic and environmental factors. OBJECTIVE: The objective of the study was to localize genes contributing to bone mineral density (BMD) variation. DESIGN: An autosomal genome-wide scan for BMD at the lumbar spine and femoral neck was conducted with variance components linkage methods. PARTICIPANTS: A total of 103 pedigrees (Network in Europe on Male Osteoporosis Family Study) ascertained through a male relative with low (Z-score < or = -2) BMD values at either lumbar spine or femoral neck. MAIN OUTCOME MEASURES: Nonparametric multipoint logarithm of the odds ratio scores for lumbar spine and femoral neck BMD values adjusted for age, gender, and body mass index. RESULTS: We identified a total of eight chromosomal regions with logarithm of the odds ratio score of 1.5 or greater (P < or = 5 x 10(-3)): on 1q42-43, 11q12-13, 12q23-24, 17q21-23, 21q22, and 22q11 for lumbar spine and on 5q31-33 and 13q12-14 for femoral neck BMD. CONCLUSIONS: Four of our detected quantitative trait loci (QTL) reached the genome-wide criteria for significant (17q,21-23, P < or = 2 x 10(-5)) or suggestive (11q12-13, 22q11, and 13q12-14, P < or = 7 x 10(-4)) linkage. Apart from 22q11, which is a novel QTL, all other loci provide consistent replication for previously reported QTLs for BMD and other bone-related traits. Finally, several of our specific-linkage areas encompass prominent candidate genes: type 1 collagen (COL1A1) and the sclerosteosis/van Buchem disease (SOST) genes on 17q21-23; the low-density lipoprotein receptor-related protein 5 (LRP5) gene on 11q12-13; and the rank ligand gene on 13q12-14. Further analysis of these positive regions by fine linkage disequilibrium mapping is thus warranted.
Authors: Ching-Lung Cheung; Gregory Livshits; Yanhua Zhou; James B Meigs; Jarred B McAteer; Jose C Florez; L Adrienne Cupples; Serkalem Demissie; Douglas P Kiel; David Karasik Journal: J Bone Miner Res Date: 2010-07 Impact factor: 6.741
Authors: David Karasik; Josée Dupuis; Kelly Cho; L Adrienne Cupples; Yanhua Zhou; Douglas P Kiel; Serkalem Demissie Journal: Bone Date: 2010-01-11 Impact factor: 4.398
Authors: Ruixue Hou; Shelley A Cole; Mariaelisa Graff; Karin Haack; Sandra Laston; Anthony G Comuzzie; Nitesh R Mehta; Kathleen Ryan; Diana L Cousminer; Babette S Zemel; Struan F A Grant; Braxton D Mitchell; Roman J Shypailo; Margaret L Gourlay; Kari E North; Nancy F Butte; V Saroja Voruganti Journal: Bone Date: 2019-11-29 Impact factor: 4.398