UNLABELLED: Using autosome-wide linkage analysis in 964 Amish, strong evidence was found for the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22 (LOD = 4.15 and 3.36, respectively). INTRODUCTION: BMD is highly heritable, with genetic factors accounting for 60-88% of variation. The goal of this study was to localize genes contributing to BMD variation. MATERIALS AND METHODS: The Amish Family Osteoporosis Study was designed to identify genes affecting bone health. The Amish are a genetically closed population with a homogeneous lifestyle. BMD was measured at the spine, hip, and radius using DXA in 964 participants (mean age, 50.2 +/- 16.3 [SD] years; range, 18-99 years) from large multigenerational families. Genotyping of 731 highly polymorphic microsatellite markers (average spacing of 5.4 cM) and autosome-wide multipoint linkage analysis were performed. RESULTS: In the overall study population, no strong evidence for linkage was detected to any chromosomal region (peak LOD: 2.11 for radius BMD on chromosome 3q26). In a subgroup analysis of men (n = 371), strong evidence was detected for a quantitative trait locus (QTL) influencing BMD variation on chromosome 7q31 at the total hip (LOD = 4.15) and femoral neck (LOD = 3.09) and for a second QTL influencing spine BMD at 21q22 (LOD = 3.36). Suggestive evidence of linkage was found in men for a QTL at 12q24 affecting total hip BMD (LOD = 2.60) and at 18p11 for femoral neck (LOD = 2.07), and in women (n = 593) at 1p36 for femoral neck BMD (LOD = 2.02) and at 1q21 for spine BMD (LOD = 2.11). In age subgroup analyses, suggestive evidence for linkage was found for those <50 years of age (n = 521) on chromosomes 11q22 and 14q23 (LODs = 2.11 and 2.16, respectively) and for those >50 years of age (n = 443) on 3p25.2 (LOD = 2.32). CONCLUSIONS: These results strongly suggest the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22. Modest evidence was found for genes affecting BMD in women on chromosomes 1p36 and 1q21 and in men at 12q24, replicating results from other populations.
UNLABELLED: Using autosome-wide linkage analysis in 964 Amish, strong evidence was found for the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22 (LOD = 4.15 and 3.36, respectively). INTRODUCTION: BMD is highly heritable, with genetic factors accounting for 60-88% of variation. The goal of this study was to localize genes contributing to BMD variation. MATERIALS AND METHODS: The Amish Family Osteoporosis Study was designed to identify genes affecting bone health. The Amish are a genetically closed population with a homogeneous lifestyle. BMD was measured at the spine, hip, and radius using DXA in 964 participants (mean age, 50.2 +/- 16.3 [SD] years; range, 18-99 years) from large multigenerational families. Genotyping of 731 highly polymorphic microsatellite markers (average spacing of 5.4 cM) and autosome-wide multipoint linkage analysis were performed. RESULTS: In the overall study population, no strong evidence for linkage was detected to any chromosomal region (peak LOD: 2.11 for radius BMD on chromosome 3q26). In a subgroup analysis of men (n = 371), strong evidence was detected for a quantitative trait locus (QTL) influencing BMD variation on chromosome 7q31 at the total hip (LOD = 4.15) and femoral neck (LOD = 3.09) and for a second QTL influencing spine BMD at 21q22 (LOD = 3.36). Suggestive evidence of linkage was found in men for a QTL at 12q24 affecting total hip BMD (LOD = 2.60) and at 18p11 for femoral neck (LOD = 2.07), and in women (n = 593) at 1p36 for femoral neck BMD (LOD = 2.02) and at 1q21 for spine BMD (LOD = 2.11). In age subgroup analyses, suggestive evidence for linkage was found for those <50 years of age (n = 521) on chromosomes 11q22 and 14q23 (LODs = 2.11 and 2.16, respectively) and for those >50 years of age (n = 443) on 3p25.2 (LOD = 2.32). CONCLUSIONS: These results strongly suggest the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22. Modest evidence was found for genes affecting BMD in women on chromosomes 1p36 and 1q21 and in men at 12q24, replicating results from other populations.
Authors: Nicole Hoppman; John C McLenithan; Daniel J McBride; Haiqing Shen; Jan Bruder; Richard L Bauer; John R Shaffer; Jie Liu; Elizabeth A Streeten; Alan R Shuldiner; Candace M Kammerer; Braxton D Mitchell Journal: Bone Date: 2010-05-05 Impact factor: 4.398
Authors: Carrie E Bearden; David C Glahn; Agatha D Lee; Ming-Chang Chiang; Theo G M van Erp; Tyrone D Cannon; Allan L Reiss; Arthur W Toga; Paul M Thompson Journal: Biol Psychol Date: 2008-02-23 Impact factor: 3.251
Authors: Enda M Byrne; Uttam K Raheja; Sarah H Stephens; Andrew C Heath; Pamela A F Madden; Dipika Vaswani; Gagan V Nijjar; Kathleen A Ryan; Hassaan Youssufi; Philip R Gehrman; Alan R Shuldiner; Nicholas G Martin; Grant W Montgomery; Naomi R Wray; Elliot C Nelson; Braxton D Mitchell; Teodor T Postolache Journal: J Clin Psychiatry Date: 2015-02 Impact factor: 4.384
Authors: Wesley G Beamer; Kathryn L Shultz; Harold F Coombs; Lindsay G Horton; Leah Rae Donahue; Clifford J Rosen Journal: J Bone Miner Res Date: 2012-01 Impact factor: 6.741
Authors: Imranul Alam; Qiwei Sun; Lixiang Liu; Daniel L Koller; Lucinda G Carr; Michael J Econs; Tatiana Foroud; Charles H Turner Journal: J Bone Miner Res Date: 2008-06 Impact factor: 6.741
Authors: Woei-Jyh Lee; Toni I Pollin; Jeffrey R O'Connell; Richa Agarwala; Alejandro A Schäffer Journal: BMC Med Genet Date: 2010-05-02 Impact factor: 2.103
Authors: Cristopher V Van Hout; Albert M Levin; Evadnie Rampersaud; Haiqing Shen; Jeffrey R O'Connell; Braxton D Mitchell; Alan R Shuldiner; Julie A Douglas Journal: Genet Epidemiol Date: 2010-02 Impact factor: 2.135
Authors: Claudine G James; Lee-Anne Stanton; Hanga Agoston; Veronica Ulici; T Michael Underhill; Frank Beier Journal: PLoS One Date: 2010-01-13 Impact factor: 3.240