title: The obesity-risk variant of FTO is inversely related with the So-Eum constitutional type: genome-wide association and replication analyses.
abstract: BACKGROUND
  Body constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types.
  
  
  METHODS
  We conducted GWA analysis and followed replication analysis in two large populations (5,490 subjects: 3,810 subjects at discovery stage and 1,680 subjects at replication stage) to identify the replicable constitution-associated variants, wherein subjects with the highest tertile of constitution probability values versus the reference with the lowest tertile of the values obtained from a recently developed constitution analysis tool were compared.
  
  
  RESULTS
  We found that the obesity-risk variant in intron 1 of the fat mass and obesity-associated (FTO) gene was replicably inversely associated with the So-Eum (SE) type, characterized by reduced appetite, slim body, and cautious personality (rs7193144 in combined samples: odds ratio = 0.729, p = 1.47 × 10(-7)), and substantial association signal remained after controlling for body mass index (BMI). In contrast, the association of the variant with the Tae-Eum type, characterized by high body mass, disappeared after controlling BMI.
  
  
  CONCLUSIONS
  In summary, the obesity-risk variant in FTO intron 1 was inversely associated with the SE type, independent of BMI, which corresponded well with the characteristics of the SE type, such as the lowest body mass and lowest susceptibility to metabolic disorders among the constitutional types. Therefore, the obesity-risk variant of FTO associated with body mass increase might be involved in the determination of body constitution type.
authors.affiliation: KM Health Technology Research Group, Medical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. scha@kiom.re.kr.
authors.forename: Seongwon
authors.initials: S
authors.lastname: Cha
authors.affiliation: KM Health Technology Research Group, Medical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. yuhyunjoo@naver.com.
authors.forename: Hyunjoo
authors.initials: H
authors.lastname: Yu
authors.affiliation: KM Health Technology Research Group, Medical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. dkdus2000@kiom.re.kr.
authors.forename: Ah Yeon
authors.initials: AY
authors.lastname: Park
authors.affiliation: KM Health Technology Research Group, Medical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. sooao@kiom.re.kr.
authors.forename: Soo A
authors.initials: SA
authors.lastname: Oh
authors.affiliation: Medical Engineering R&D Group, Medical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 305-811, Republic of Korea. ssmed@kiom.re.kr.
authors.forename: Jong Yeol
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000368:Aged; D001824:Body Constitution / Q000235:genetics; D015992:Body Mass Index; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D055670:Medicine, Korean Traditional; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D012307:Risk Factors; D013008:Somatotypes / Q000235:genetics*