Title Page

Contents

Abstract 10

Introduction 13

Methods 15

1. Study subjects 15

2. Genotyping, Quality Control, and Imputation 15

3. Phenotyping 16

4. Statistical analyses 17

Results 18

1. Identification of genetic variants associated with MetS and related traits 18

2. Quantification of genome-wide genetic correlation between MetS and related traits 19

3. Inference of causal relationship between MetS and related traits 19

Discussion 21

Figure and Table Legends 24

Reference 54

KOREAN ABSTRACT 59

Table 1. Clinical statistics of subjects for MetS in the KBA dataset 33

Table 2. Association of MetS SNPs with related traits 34

Table 3. Genome-wide genetic correlation between MetS and related diseases 35

Table 4. Genome-wide genetic correlation between MetSand related QTs 36

Supplementary Table 1. Clinical statistics of subjects for MetS related diseases in the KBA dataset 37

Supplementary Table 2. Genetic variants showing evidence of suggestive association with MetS 38

Supplementary Table 3. Genetic variants showing evidence of suggestive association with obesity 39

Supplementary Table 4. Genetic variants showing evidence of suggestive association with T2D 40

Supplementary Table 5. Genetic variants showing evidence of suggestive association with dyslipidemia 41

Supplementary Table 6. Genetic variants showing evidence of suggestive association with hypertension 42

Supplementary Table 7. Genetic variants showing evidence of suggestive association with BMI 43

Supplementary Table 8. Genetic variants showing evidence of suggestive association with WC 44

Supplementary Table 9. Genetic variants showing evidence of suggestive association with TG 45

Supplementary Table 10. Genetic variants showing evidence of suggestive association with HDLC 46

Supplementary Table 11. Genetic variants showing evidence of suggestive association with LDLC 47

Supplementary Table 12. Genetic variants showing evidence of suggestive association with TCHL 48

Supplementary Table 13. Genetic variants showing evidence of suggestive association with FPG 49

Supplementary Table 14. Genetic variants showing evidence of suggestive association with HbA1C 50

Supplementary Table 15. Genetic variants showing evidence of suggestive association with SBP 51

Supplementary Table 16. Genetic variants showing evidence of suggestive association with DBP 52

Supplementary Table 17. Genome-wide genetic correlation between metabolic disease and related QTs 53

Figure 1. Genetic correlation between MetS and related diseases 28

Figure 2. Genetic correlation between MetS and related QTs 29

Figure 3. Outline of MR analysis 30

Figure 4. MR between MetS and related diseases 31

Figure 5. MR between MetS and related QTs 32