Age, gender, and body mass effects on quantitative trait loci for bone mineral density: the Framingham Study
Age, gender, and body mass effects on quantitative trait loci for bone mineral density: the Framingham Study
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DOI：
10.1016/s8756-3282(03)00173-x
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发表时间：
2003-09-01
期刊：
影响因子：
4.1
通讯作者：
Kiel, DP
中科院分区：
文献类型：
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作者：
Karasik, D;Cupples, LA;Kiel, DP
对弗雷明翰骨质疏松症研究的参与者(330个家系中的1557名成员，主要是高加索人)进行了全基因组扫描，401个微卫星标记的平均间距为10 cM。用DXA测量股骨颈、粗隆、Ward‘s区和腰椎的骨密度(BMD)。我们最近的研究(J bone Mines Res 17(2002)，1718)报告了一些与可能的数量性状基因座(QTL)有关联的区域。目前的研究根据性别、年龄和体重指数(BMI)的已知生物学因素，在我们家系的亚样本中估计了这些区域的连锁异质性。家系样本按性别[男性(年龄35-96岁)，女性(29-91岁)]，年龄[60岁或以下(29-60岁)和60岁以上(61-96岁)]和BMI[按BMI分为低BMI或高BMI，男性27.7(BMI 17-53)和女性25.8(14-54)]分为三组。子样本中BMD的遗传度估计(根据年龄、人体测量、营养、体力活动和女性的雌激素使用进行了调整)介于0.47到0.69之间。子样本中BMD的两点和多点方差分量连锁分析(使用SOLAR)支持了先前在总样本中8q24.13和14q31(LODS>；2.0)报道的连锁结果的结果。然而，在6p21.2和21qter上观察到了连锁的异质性，其中总样本中的结果不被亚样本支持。另一方面，在4q34.1(男性)、9q22-9q31(年轻)、16p13.2(高体重指数)和17p13.3(年龄较大)上发现了亚样本特异性最大值，这些结果没有在总样本结果中反映出来。总之，QTL效应在按性别、年龄和BMI分层的家系成员中表现出异质性；在某些情况下，在亚组中发现了新的基因座。这些发现可能表明，基因对骨密度测定的影响在男性和女性、年轻人和老年人以及苗条和肥胖的成年人之间存在差异。在骨量遗传学研究中，可能需要对按同质组分层的家庭成员进行评估。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
A genome-wide scan was performed in participants from the Framingham Osteoporosis Study (1557 members of 330 mostly Caucasian pedigrees), with 401 microsatellite markers spaced on average at 10 cM. Bone mineral density (BMD) was measured at the femoral neck, trochanter, Ward's area, and lumbar spine with DXA. Our recent study (J Bone Mines Res 17 (2002), 1718) reported a number of regions with suggestive linkage to possible quantitative trait loci (QTL). The current study estimates the heterogeneity of linkage in these regions in subsamples of our pedigrees, stratified on the known biological contributors to bone mass of sex, age, and body mass index (BMI). The pedigree sample was stratified into three sets of subgroups by sex [males (age range 35-96 years), females (29-91 years)], by age [60 or younger (29-60 years) and older than 60 (61-96 years)], and by BMI [stratified into low or high BMI, by median cut-off 27.7 in males (BMI range 17-53) and 25.8 in females (14-54)]. Heritability estimates of BMD (adjusted for age, anthropometry, nutrition, physical activity, and, in females, estrogen use) in subsamples ranged from 0.47 to 0.69. Two-point and multipoint variance component linkage analyses of BMD (using SOLAR) in subsamples supported findings of previously reported suggestive linkage results in the total sample on 8q24.13 and 14q31 (LODs > 2.0). However, heterogeneity of linkage was observed on 6p21.2 and 21qter, where findings in the total sample were not supported by subsamples. On the other hand, subsample-specific maxima were found, on 4q34.1 (males), 9q22-9q31 (younger), 16p13.2 (high BMI), and 17p13.3 (older), which were not reflected by the total sample results. In conclusion, heterogeneity of QTL effects was revealed in pedigree members stratified by sex, age, and BMI; in some instances new loci were identified in subgroups. These findings may suggest that effects of genes on the determination of BMD differ between men and women, younger and older, and lean and obese adults. Evaluation of family members stratified in homogeneous groups may be warranted in genetic studies of bone mass. (C) 2003 Elsevier Science (USA). All rights reserved.