Ralston Stuart H, Galwey Nick, MacKay Ian, Albagha Omar M E, Cardon Lon, Compston Juliet E, Cooper Cyrus, Duncan Emma, Keen Richard, Langdahl Bente, McLellan Alastair, O'Riordan Jeffrey, Pols Huibert A, Reid David M, Uitterlinden Andre G, Wass John, Bennett Simon T
Rheumatic Diseases Unit, University of Edinburgh Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.
Hum Mol Genet. 2005 Apr 1;14(7):943-51. doi: 10.1093/hmg/ddi088. Epub 2005 Mar 3.
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 < or =50 years) and two suggestive QTL for LS-BMD on chromosomes 18p11 (LOD score +2.83; women >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.
骨质疏松症是一种常见疾病，具有很强的遗传因素，其特征是骨量减少和骨折风险增加。骨矿物质密度（BMD）是一种高度可遗传的性状，也是骨质疏松性骨折风险的关键决定因素，但相关基因尚未完全明确。在此，我们通过全基因组扫描确定了调节BMD的数量性状基因座（QTL），该扫描涉及来自715个家庭的3691名个体，这些个体因先证者腰椎（LS - BMD）或股骨颈（FN - BMD）的BMD值降低而被选中。在整个研究组中进行了连锁分析，并对年龄、性别、体重和身高进行了校正。分别对男性和女性进行了进一步分析，以确定性别特异性QTL，对50岁以下和50岁以上的人群进行分析，以区分峰值骨量的QTL和影响老年人骨量的QTL。当对所有受试者的数据进行综合分析时，未发现提示性或显著连锁的区域。然而，在亚组分析中，我们在10q21染色体上确定了一个与FN - BMD相关的显著QTL（LOD分数 +4.42；男性≤50岁），在18p11染色体上确定了两个与LS - BMD相关的提示性QTL（LOD分数 +2.83；女性＞50岁）和20q13染色体上的提示性QTL（LOD分数 +3.20；女性≤50岁）。我们在3q25、4q25、7p14、16p13和16q23染色体上确定了另外五个与BMD相关的QTL，其LOD分数大于 +2.20。本研究为调节人类BMD的性别特异性、部位特异性和年龄特异性QTL提供了证据，并说明了进行亚组分析以检测这些基因座的重要性。
