PT  - JOURNAL ARTICLE
AU  - Yi Li
AU  - Yi Wang
AU  - Menghan Zhang
AU  - Yanyun Ma
AU  - Kun Wang
AU  - Xiaoyu Liu
AU  - Meng Hao
AU  - Chang Sun
AU  - Xiaofeng Wang
AU  - Xingdong Chen
AU  - Yao Zhang
AU  - Wenyuan Duan
AU  - Longli Kang
AU  - Bin Qiao
AU  - Jiucun Wang
AU  - Li Jin
TI  - Using composite phenotypes to reveal hidden physiological heterogeneity and model oxygen saturation variation of high altitude acclimatization in a Chinese Han longitudinal cohort
AID  - 10.1101/336446
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 336446
4099  - http://biorxiv.org/content/early/2018/06/12/336446.short
4100  - http://biorxiv.org/content/early/2018/06/12/336446.full
AB  - Altitude acclimatization is the physiological process of the human body adjusting to the decreased availability of oxygen. Since several physiological processes are involved and the relation among them is complicated, analyses of single-traits is insufficient in revealing the complex mechanism of high altitude acclimatization. In this study, we examined whether these physiological responses could be studied as composite phenotypes which are represented by a linear combination of physiological traits. We developed a strategy which combines both spectral clustering and Partial Least Squares Path Modeling (PLSPM) to define composite phenotypes based on a cohort study of 883 Chinese Han males. And we captured 14 composite phenotypes from 28 physiological traits of high altitude acclimatization. Using these composite phenotypes, we applied k-means clustering to reveal hidden population physiological heterogeneity in high altitude acclimatization. Furthermore, we employed multivariate linear regression to systematically model (Model 1 and Model 2) oxygen saturation (SpO2) changes in high altitude acclimatization and evaluated the model fitness performance. And composite phenotypes based Model 2 has better fitness than single-traits based Model 1 in all measurement indices. Therefore, this new strategy of defining and applying composite phenotypes can be considered as a general strategy of complex traits research, which may also shed light on genetic loci discovery and phenome analyses.