We conducted a comprehensive genetic investigation of obesity in a cohort of 93,673 Korean individuals,categorized by body mass index and waist circumference using Korean-specific and international criteria.To explore...We conducted a comprehensive genetic investigation of obesity in a cohort of 93,673 Korean individuals,categorized by body mass index and waist circumference using Korean-specific and international criteria.To explore the genetic architecture of obesity and its related comorbidities,we performed genome-wide association studies and constructed polygenic risk scores(PRSs)using both conventional single-trait and advanced multiple-trait models,including the PRSsum approach.Our analyses identified genome-wide significant loci and demonstrated their higher heritability for general obesity than for abdominal obesity,and for moderate obesity than for severe obesity.East Asian populations showed stronger genetic correlations between abdominal obesity and obesity-related diseases.Both single-trait and multiple-trait PRSs stratified individuals by risk,with low-PRS individuals exhibiting reduced risk for obesity,hypertension,and type 2 diabetes,while high-PRS individuals displayed elevated risk,particularly under the multiple-trait model.Interaction and mediation analyses revealed distinct genetic pathways through which obesity contributes to disease development.Collectively,our findings revealed key loci and shared genetic mechanisms linking obesity and its comorbidities in the Korean population.These insights highlight the value of multiple-trait PRS models and underscore the importance of ancestry-specific genetic research for addressing the obesity epidemic.展开更多
基金National Biobank of Korea,the Korea Disease Control and Prevention Agency,Republic of Korea(Grant No.KBN-2020-101)supported by the National Research Foundation(NRF)of Korea funded by the Korean government(MSIT)(Grant No.RS-2024-00346850)+2 种基金the Bio&Medical Technology Development Program of the NRF funded by the Korean government(MSIT)(Grant No.RS-2025-16063949)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(Grant No.RS-2024-00403700)supported by the National Supercomputing Center,Korea Institute of Science&Technology Information(KISTI),with supercomputing resources including technical support(Grant Nos.KSC-2022-CRE-0319 and KSC-2023-CRE-0117).
文摘We conducted a comprehensive genetic investigation of obesity in a cohort of 93,673 Korean individuals,categorized by body mass index and waist circumference using Korean-specific and international criteria.To explore the genetic architecture of obesity and its related comorbidities,we performed genome-wide association studies and constructed polygenic risk scores(PRSs)using both conventional single-trait and advanced multiple-trait models,including the PRSsum approach.Our analyses identified genome-wide significant loci and demonstrated their higher heritability for general obesity than for abdominal obesity,and for moderate obesity than for severe obesity.East Asian populations showed stronger genetic correlations between abdominal obesity and obesity-related diseases.Both single-trait and multiple-trait PRSs stratified individuals by risk,with low-PRS individuals exhibiting reduced risk for obesity,hypertension,and type 2 diabetes,while high-PRS individuals displayed elevated risk,particularly under the multiple-trait model.Interaction and mediation analyses revealed distinct genetic pathways through which obesity contributes to disease development.Collectively,our findings revealed key loci and shared genetic mechanisms linking obesity and its comorbidities in the Korean population.These insights highlight the value of multiple-trait PRS models and underscore the importance of ancestry-specific genetic research for addressing the obesity epidemic.
