TY - JOUR
T1 - Identification of genetic variants for female obesity and evaluation of the causal role of genetically defined obesity in polycystic ovarian syndrome
AU - Ahn, Yeongseon
AU - Lee, Hyejin
AU - Cho, Yoon Shin
N1 - Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) Grant (NRF-2020R1I1A2075302) and Hallym University Research Fund 2020 (HRF-202002-008).
Publisher Copyright:
© 2020 Ahn et al.
PY - 2020
Y1 - 2020
N2 - Purpose: Observational studies have demonstrated an increased risk of polycystic ovarian syndrome (PCOS) in obese women. This study aimed to identify genetic variants influencing obesity in females and to evaluate the causal association between genetically defined obesity and PCOS in Korean women. Methods: Two-stage GWAS was conducted to identify genetic variants influencing obesity traits (such as body mass index [BMI], waist–hip ratio [WHR], and waist circumference [WC]) in Korean women. Two-sample Mendelian randomization (MR) analysis was employed to evaluate the causal effect of variants as genetic instruments for female obesity on PCOS. Results: Meta-analysis of 9953 females combining discovery (N = 4658) and replication (N = 5295) stages detected four (rs11162584, rs6760543, rs828104, rs56137030), six (rs139702234, rs2341967, rs73059848, rs5020945, rs550532151, rs61971548), and two genetic variants (rs7722169, rs7206790) suggesting a highly significant association (P < 1×10−6) with BMI, WHR, and WC, respectively. Of these, an intron variant rs56137030 in FTO achieved genome-wide significant association (P = 3.39×10−8) with BMI in females. Using variants for female obesity, their effect on PCOS in 946 cases and 976 controls was evaluated by MR analysis. MR results indicated no significant association between genetically defined obesity and PCOS in Korean women. Conclusion: This study, for the first time, revealed genetic variants for female obesity in the Korean population and reported no causal association between genetically defined obesity and PCOS in Korean women.
AB - Purpose: Observational studies have demonstrated an increased risk of polycystic ovarian syndrome (PCOS) in obese women. This study aimed to identify genetic variants influencing obesity in females and to evaluate the causal association between genetically defined obesity and PCOS in Korean women. Methods: Two-stage GWAS was conducted to identify genetic variants influencing obesity traits (such as body mass index [BMI], waist–hip ratio [WHR], and waist circumference [WC]) in Korean women. Two-sample Mendelian randomization (MR) analysis was employed to evaluate the causal effect of variants as genetic instruments for female obesity on PCOS. Results: Meta-analysis of 9953 females combining discovery (N = 4658) and replication (N = 5295) stages detected four (rs11162584, rs6760543, rs828104, rs56137030), six (rs139702234, rs2341967, rs73059848, rs5020945, rs550532151, rs61971548), and two genetic variants (rs7722169, rs7206790) suggesting a highly significant association (P < 1×10−6) with BMI, WHR, and WC, respectively. Of these, an intron variant rs56137030 in FTO achieved genome-wide significant association (P = 3.39×10−8) with BMI in females. Using variants for female obesity, their effect on PCOS in 946 cases and 976 controls was evaluated by MR analysis. MR results indicated no significant association between genetically defined obesity and PCOS in Korean women. Conclusion: This study, for the first time, revealed genetic variants for female obesity in the Korean population and reported no causal association between genetically defined obesity and PCOS in Korean women.
KW - Causal relation
KW - Female obesity
KW - Genome-wide association study
KW - Mendelian randomization
KW - Polycystic ovarian syndrome
UR - http://www.scopus.com/inward/record.url?scp=85096069369&partnerID=8YFLogxK
U2 - 10.2147/DMSO.S281529
DO - 10.2147/DMSO.S281529
M3 - Article
AN - SCOPUS:85096069369
SN - 1178-7007
VL - 13
SP - 4311
EP - 4322
JO - Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
JF - Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
ER -