Genetic Architecture Associated With Familial Short Stature

Abstract

Context Human height is an inheritable, polygenic trait under complex and multi-locus genetic regulation. Familial short stature (FSS; also called genetic short stature) is the most common type of short stature and is insufficiently known. Objective To investigate the FSS genetic profile and develop a polygenic risk predisposition score for FSS risk prediction. Design and Setting The FSS case group of Han Chinese ancestry was diagnosed by pediatric endocrinologists in Taiwan. Patients and Interventions The genetic profile of 1,163 FSS cases was identified by using a bootstrapping sub-sampling and genome-wide association studies (GWAS) method. Main Outcome Measures Genetic profile, polygenic risk predisposition score for risk prediction. Results Ten novel genetic SNPs and 9 reported GWAS human height-related SNPs were identified for FSS risk. These 10 novel SNPs served as a polygenic risk predisposition score for FSS risk prediction (area under curve (AUC): 0.940 in the testing group). This FSS polygenic risk predisposition score was also associated with the height reduction regression tendency in the general population. Conclusion A polygenic risk predisposition score composed of 10 genetic SNPs is useful for FSS risk prediction and the height reduction tendency. Thus, it might contribute to FSS risk in the Han Chinese population from Taiwan.