Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population
Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11560 |
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| author | Nara Yoon Yoon Shin Cho |
| author_facet | Nara Yoon Yoon Shin Cho |
| author_sort | Nara Yoon |
| collection | DOAJ |
| description | Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean population. For this purpose, we obtained base data resulting from a GWAS on BMI using 57,110 HEXA study subjects from the Korean Genome and Epidemiology Study (KoGES). Subsequently, we calculated PRSs in 13,504 target subjects from the KARE and CAVAS studies of KoGES using the PRSice-2 software. The best-fit PRS for BMI (PRS<sub>BMI</sub>) comprising 53,341 SNPs was selected at a <i>p</i>-value threshold of 0.064, at which the model fit had the greatest <i>R</i><sup>2</sup> score. The PRS<sub>BMI</sub> was tested for its association with obesity-related quantitative traits and diseases in the target dataset. Linear regression analyses demonstrated significant associations of PRS<sub>BMI</sub> with BMI, blood pressure, and lipid traits. Logistic regression analyses revealed significant associations of PRS<sub>BMI</sub> with obesity, hypertension, and hypo-HDL cholesterolemia. We observed about 2-fold, 1.1-fold, and 1.2-fold risk for obesity, hypertension, and hypo-HDL cholesterolemia, respectively, in the highest-risk group in comparison to the lowest-risk group of PRS<sub>BMI</sub> in the test population. We further detected approximately 26.0%, 2.8%, and 3.9% differences in prevalence between the highest and lowest risk groups for obesity, hypertension, and hypo-HDL cholesterolemia, respectively. To predict the incidence of obesity and related diseases, we applied PRS<sub>BMI</sub> to the 16-year follow-up data of the KARE study. Kaplan–Meier survival analysis showed that the higher the PRS<sub>BMI</sub>, the higher the incidence of dyslipidemia and hypo-HDL cholesterolemia. Taken together, this study demonstrated that a PRS developed for BMI may be a valuable indicator to assess the risk of obesity and related diseases in the Korean population. |
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| language | English |
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| spelling | doaj.art-0b1e618a9d16465ebf0dc538064d0f532023-11-18T19:41:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141156010.3390/ijms241411560Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean PopulationNara Yoon0Yoon Shin Cho1Department of Biomedical Science, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Biomedical Science, Hallym University, Chuncheon 24252, Republic of KoreaHundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean population. For this purpose, we obtained base data resulting from a GWAS on BMI using 57,110 HEXA study subjects from the Korean Genome and Epidemiology Study (KoGES). Subsequently, we calculated PRSs in 13,504 target subjects from the KARE and CAVAS studies of KoGES using the PRSice-2 software. The best-fit PRS for BMI (PRS<sub>BMI</sub>) comprising 53,341 SNPs was selected at a <i>p</i>-value threshold of 0.064, at which the model fit had the greatest <i>R</i><sup>2</sup> score. The PRS<sub>BMI</sub> was tested for its association with obesity-related quantitative traits and diseases in the target dataset. Linear regression analyses demonstrated significant associations of PRS<sub>BMI</sub> with BMI, blood pressure, and lipid traits. Logistic regression analyses revealed significant associations of PRS<sub>BMI</sub> with obesity, hypertension, and hypo-HDL cholesterolemia. We observed about 2-fold, 1.1-fold, and 1.2-fold risk for obesity, hypertension, and hypo-HDL cholesterolemia, respectively, in the highest-risk group in comparison to the lowest-risk group of PRS<sub>BMI</sub> in the test population. We further detected approximately 26.0%, 2.8%, and 3.9% differences in prevalence between the highest and lowest risk groups for obesity, hypertension, and hypo-HDL cholesterolemia, respectively. To predict the incidence of obesity and related diseases, we applied PRS<sub>BMI</sub> to the 16-year follow-up data of the KARE study. Kaplan–Meier survival analysis showed that the higher the PRS<sub>BMI</sub>, the higher the incidence of dyslipidemia and hypo-HDL cholesterolemia. Taken together, this study demonstrated that a PRS developed for BMI may be a valuable indicator to assess the risk of obesity and related diseases in the Korean population.https://www.mdpi.com/1422-0067/24/14/11560obesitybody mass indexpolygenic risk scoresingle-nucleotide polymorphismgenome-wide association studydisease risk assessment |
| spellingShingle | Nara Yoon Yoon Shin Cho Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population International Journal of Molecular Sciences obesity body mass index polygenic risk score single-nucleotide polymorphism genome-wide association study disease risk assessment |
| title | Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population |
| title_full | Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population |
| title_fullStr | Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population |
| title_full_unstemmed | Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population |
| title_short | Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population |
| title_sort | development of a polygenic risk score for bmi to assess the genetic susceptibility to obesity and related diseases in the korean population |
| topic | obesity body mass index polygenic risk score single-nucleotide polymorphism genome-wide association study disease risk assessment |
| url | https://www.mdpi.com/1422-0067/24/14/11560 |
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