Objective: Sasang constitutional medicine is a traditional Korean medicine, in which an individual is
classified into one of four types of constitution: Taeum (TE), Soeum (SE) Soyang (SY), and Taeyang
(TY). These constitution types are determined with biological and physiological characteristics, so it
has been assumed that genetic factors are associated with each constitution type. Identifying the
genetic elements underlying each constitution is necessary for the elucidation of the molecular
mechanism of Sasang constitutional medicine.
Design: A total of 341,998 genetic loci across the whole genome were genotyped for 1,222 subjects of
defined constitution type. The genetic loci associated with each constitution type were identified and
the functional connectivity of genes within these loci was analyzed using statistical text mining.
Results: From the difference in allele frequencies between constitution types, we identified significant
genetic loci associated with each type. Chromosomes 3q27.3 (rs10937331, p=2.71×10-6), 15q22.2
(rs7180547, p=1.58×10-6), and 14q22.3 (rs12431592, p=1.31×10-6) were most significantly associated
with TE, SE, and SY constitution types, respectively. From the functional relationship analysis using
all loci with a p-value ≤10-4, genes associated with each constitution type were identified. Fifteen
genes, including GPM6A, SYT4, and GRIK1, were significantly associated with the TE constitution
type (p<0.05); 12 genes, including DRGX and AKAP11, were significantly associated with the SE
constitution type (p<0.05); and 17 genes, including ZFP42, CDH22, ALDH1A2, OTX2, and EN2,
were significantly associated with the SY constitution type (p<0.05).
Conclusions: Genetic loci and genes associated with Sasang constitution types were systematically
identified from a genome-wide association study using a large number of subjects. |
