INTRODUCTION: A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. METHODS: aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). RESULTS: A genome wide scan identified significant QTL (LOD>3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. CONCLUSIONS: This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.
INTRODUCTION: A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. METHODS: aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). RESULTS: A genome wide scan identified significant QTL (LOD>3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. CONCLUSIONS: This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.
Authors: Munro Peacock; Daniel L Koller; Siu Hui; C Conrad Johnston; Tatiana Foroud; Michael J Econs Journal: Osteoporos Int Date: 2004-03-16 Impact factor: 4.507
Authors: A C Looker; H W Wahner; W L Dunn; M S Calvo; T B Harris; S P Heyse; C C Johnston; R L Lindsay Journal: Osteoporos Int Date: 1995 Impact factor: 4.507
Authors: Stuart H Ralston; Nick Galwey; Ian MacKay; Omar M E Albagha; Lon Cardon; Juliet E Compston; Cyrus Cooper; Emma Duncan; Richard Keen; Bente Langdahl; Alastair McLellan; Jeffrey O'Riordan; Huibert A Pols; David M Reid; Andre G Uitterlinden; John Wass; Simon T Bennett Journal: Hum Mol Genet Date: 2005-03-03 Impact factor: 6.150
Authors: M Devoto; K Shimoya; J Caminis; J Ott; A Tenenhouse; M P Whyte; L Sereda; S Hall; E Considine; C J Williams; G Tromp; H Kuivaniemi; L Ala-Kokko; D J Prockop; L D Spotila Journal: Eur J Hum Genet Date: 1998 Mar-Apr Impact factor: 4.246
Authors: Imranul Alam; Daniel L Koller; Qiwei Sun; Ryan K Roeder; Toni Cañete; Gloria Blázquez; Regina López-Aumatell; Esther Martínez-Membrives; Elia Vicens-Costa; Carme Mont; Sira Díaz; Adolf Tobeña; Alberto Fernández-Teruel; Adam Whitley; Pernilla Strid; Margarita Diez; Martina Johannesson; Jonathan Flint; Michael J Econs; Charles H Turner; Tatiana Foroud Journal: Bone Date: 2011-02-18 Impact factor: 4.398