Walker M D, Shi S, Russo J J, Liu X S, Zhou B, Zhang C, Liu G, McMahon D J, Bilezikian J P, Guo X E
Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA,
Osteoporos Int. 2014 Dec;25(12):2787-95. doi: 10.1007/s00198-014-2816-0. Epub 2014 Jul 29.
This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies.
Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies.
A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses.
The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American.
Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.
本研究采用极端表型选择法,在一组华裔美国女性和白人女性中定义了两种小梁骨表型。小梁板为主型表型在华裔美国人中更为常见,而小梁杆为主型表型在白人中更为典型。这些表型与生活方式因素关联的稳健性表明,该性状可能具有遗传基础,且这些表型可用于未来的遗传学研究。
与白人相比,通过个体小梁分割(ITS)测量时,华裔美国人具有更多板状小梁骨。这些发现提示了种族间的表型差异,这可能适合进行遗传分析。我们试图通过实施极端表型选择策略,以数字方式定义两种不同的表型——板状和杆状,从而确定在遗传研究中要研究的单一ITS板状性状,并确定所选的表型关联是否独立于生活方式因素,以便开展未来的遗传研究。
对先前描述的一组146名华裔美国女性和白人女性进行研究,她们均有高分辨率外周定量计算机断层扫描成像和ITS分析,并采用逻辑回归和受试者工作特征分析。
胫骨板与杆(TPR)比率是种族的最佳ITS鉴别指标。采用极端表型选择法,从数字上定义了两种TPR比率表型:板状为TPR比率值处于最高四分位数(≥1.336),杆状为TPR比率值处于最低四分位数(≤0.621)。具有板状表型的女性是具有杆状形态女性的25.7倍(95%置信区间7.3 - 90.1)更有可能是华裔美国人。在控制了体质和生活方式协变量后,TPR比率最高四分位数与最低四分位数的女性相比,是华裔美国人的可能性高85.0倍(95%置信区间12.7 - 568.0)。
通过极端表型选择,我们为TPR比率性状定义了板状和杆状小梁骨表型。前一种表型在华裔美国女性中更常见,而后一种表型在白人女性中更典型。在控制了体质和生活方式差异后,这些表型关联的稳健性表明TPR比率可能具有遗传基础,且本分析中定义的极端表型可用于未来研究。