Karasik D, Dupuis J, Cupples L A, Beck T J, Mahaney M C, Havill L M, Kiel D P, Demissie S
Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, 1200 Centre Street, Boston, MA 02131, USA.
Calcif Tissue Int. 2007 Sep;81(3):162-73. doi: 10.1007/s00223-007-9052-y. Epub 2007 Aug 3.
Femoral geometry and body size are both characterized by substantial heritability. The purpose of this study was to discern whether hip geometry and body size (height and body mass index, BMI) share quantitative trait loci (QTL). Dual-energy X-ray absorptiometric scans of the proximal femur from 1,473 members in 323 pedigrees (ages 31-96 years) from the Framingham Osteoporosis Study were studied. We measured femoral neck length, neck-shaft angle, subperiosteal width (outer diameter), cross-sectional bone area, and section modulus, at the narrowest section of the femoral neck (NN), intertrochanteric (IT), and femoral shaft (S) regions. In variance component analyses, genetic correlations (rho ( G )) between hip geometry traits and height ranged 0.30-0.59 and between hip geometry and BMI ranged 0.11-0.47. In a genomewide linkage scan with 636 markers, we obtained nominally suggestive linkages (bivariate LOD scores > or =1.9) for geometric traits and either height or BMI at several chromosomes (4, 6, 9, 15, and 21). Two loci, on chr. 2 (80 cM, BMI/shaft section modulus) and chr. X (height/shaft outer diameter), yielded bivariate LOD scores > or =3.0; although these loci were linked in univariate analyses with a geometric trait, neither was linked with either height or BMI. In conclusion, substantial genetic correlations were found between the femoral geometric traits, height and BMI. Linkage signals from bivariate linkage analyses of bone geometric indices and body size were similar to those obtained in univariate linkage analyses of femoral geometric traits, suggesting that most of the detected QTL primarily influence geometry of the hip.
股骨几何形状和身体大小都具有显著的遗传力。本研究的目的是确定髋部几何形状与身体大小（身高和体重指数，BMI）是否共享数量性状基因座（QTL）。我们研究了弗雷明汉骨质疏松症研究中323个家系（年龄31 - 96岁）的1473名成员近端股骨的双能X线吸收扫描。我们测量了股骨颈长度、颈干角、骨膜下宽度（外径）、横截面积和截面模量，测量部位为股骨颈（NN）、转子间（IT）和股骨干（S）区域最窄处。在方差成分分析中，髋部几何形状性状与身高之间的遗传相关性（rho (G)）范围为0.30 - 0.59，髋部几何形状与BMI之间的遗传相关性范围为0.11 - 0.47。在一项使用636个标记的全基因组连锁扫描中，我们在几条染色体（4、6、9、15和21）上获得了几何性状与身高或BMI之间名义上提示性的连锁关系（双变量LOD分数≥1.9）。位于2号染色体（80 cM，BMI/骨干截面模量）和X染色体（身高/骨干外径）上的两个基因座产生了双变量LOD分数≥3.0；尽管这些基因座在单变量分析中与一个几何性状连锁，但均未与身高或BMI连锁。总之，在股骨几何性状、身高和BMI之间发现了显著的遗传相关性。骨几何指数与身体大小的双变量连锁分析的连锁信号与股骨几何性状的单变量连锁分析中获得的信号相似，这表明大多数检测到的QTL主要影响髋部的几何形状。
