Xiaohui Ma, Lina Chang, Shuo Li, Yian Gu, Jieying Wan, Hequn Sang, Li Ding, Ming Liu, Qing He
{"title":"出生体重、儿童期和成年期体重指数与代谢功能障碍相关脂肪肝的遗传关系:孟德尔随机试验。","authors":"Xiaohui Ma, Lina Chang, Shuo Li, Yian Gu, Jieying Wan, Hequn Sang, Li Ding, Ming Liu, Qing He","doi":"10.1186/s12876-024-03383-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The causal relationship between life course adiposity with metabolic dysfunction-associated steatotic liver disease (MASLD) is ambiguous. We aimed to investigate whether there is an independent genetic causal relationship between body size at various life course and MASLD.</p><p><strong>Methods: </strong>We performed univariable and multivariable Mendelian randomization (MR) to estimate the causal effect of body size at different life stages on MASLD (i.e., defined by the clinical comprehensive diagnosis from the electronic health record [HER] codes [ICD9/ICD10] or diagnostic phrases), including birthweight, childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP).</p><p><strong>Results: </strong>In univariate analyses, higher genetically predicted lower birthweight (OR<sub>IVW</sub> = 0.61, 95%CI, 0.52 to 0.74), Childhood BMI ( OR<sub>IVW</sub> = 1.37, 95%CI, 1.12 to 1.64), and adult BMI (OR<sub>IVW</sub> = 1.41, 95%CI, 1.27 to 1.57) was significantly associated with subsequent risk of MASLD after Bonferroni correction. The MVMR analysis demonstrated compelling proof that birthweight and adult BMI had a direct causal relationship with MASLD. However, after adjusting for birthweight and adult BMI, the direct causal relationship between childhood BMI and MASLD disappeared.</p><p><strong>Conclusion: </strong>For the first time, this MR elucidated new evidence for the effect of life course adiposity on MASLD risk, providing lower birthweight and duration of obesity are independent risk factors for MASLD. Our findings indicated that weight management during distinct time periods plays a significant role in the prevention and treatment of MASLD.</p>","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351507/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetic associations of birthweight, childhood, and adult BMI with metabolic dysfunction-associated steatotic liver disease: a Mendelian randomization.\",\"authors\":\"Xiaohui Ma, Lina Chang, Shuo Li, Yian Gu, Jieying Wan, Hequn Sang, Li Ding, Ming Liu, Qing He\",\"doi\":\"10.1186/s12876-024-03383-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The causal relationship between life course adiposity with metabolic dysfunction-associated steatotic liver disease (MASLD) is ambiguous. We aimed to investigate whether there is an independent genetic causal relationship between body size at various life course and MASLD.</p><p><strong>Methods: </strong>We performed univariable and multivariable Mendelian randomization (MR) to estimate the causal effect of body size at different life stages on MASLD (i.e., defined by the clinical comprehensive diagnosis from the electronic health record [HER] codes [ICD9/ICD10] or diagnostic phrases), including birthweight, childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP).</p><p><strong>Results: </strong>In univariate analyses, higher genetically predicted lower birthweight (OR<sub>IVW</sub> = 0.61, 95%CI, 0.52 to 0.74), Childhood BMI ( OR<sub>IVW</sub> = 1.37, 95%CI, 1.12 to 1.64), and adult BMI (OR<sub>IVW</sub> = 1.41, 95%CI, 1.27 to 1.57) was significantly associated with subsequent risk of MASLD after Bonferroni correction. The MVMR analysis demonstrated compelling proof that birthweight and adult BMI had a direct causal relationship with MASLD. However, after adjusting for birthweight and adult BMI, the direct causal relationship between childhood BMI and MASLD disappeared.</p><p><strong>Conclusion: </strong>For the first time, this MR elucidated new evidence for the effect of life course adiposity on MASLD risk, providing lower birthweight and duration of obesity are independent risk factors for MASLD. Our findings indicated that weight management during distinct time periods plays a significant role in the prevention and treatment of MASLD.</p>\",\"PeriodicalId\":9129,\"journal\":{\"name\":\"BMC Gastroenterology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351507/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12876-024-03383-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12876-024-03383-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Genetic associations of birthweight, childhood, and adult BMI with metabolic dysfunction-associated steatotic liver disease: a Mendelian randomization.
Purpose: The causal relationship between life course adiposity with metabolic dysfunction-associated steatotic liver disease (MASLD) is ambiguous. We aimed to investigate whether there is an independent genetic causal relationship between body size at various life course and MASLD.
Methods: We performed univariable and multivariable Mendelian randomization (MR) to estimate the causal effect of body size at different life stages on MASLD (i.e., defined by the clinical comprehensive diagnosis from the electronic health record [HER] codes [ICD9/ICD10] or diagnostic phrases), including birthweight, childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP).
Results: In univariate analyses, higher genetically predicted lower birthweight (ORIVW = 0.61, 95%CI, 0.52 to 0.74), Childhood BMI ( ORIVW = 1.37, 95%CI, 1.12 to 1.64), and adult BMI (ORIVW = 1.41, 95%CI, 1.27 to 1.57) was significantly associated with subsequent risk of MASLD after Bonferroni correction. The MVMR analysis demonstrated compelling proof that birthweight and adult BMI had a direct causal relationship with MASLD. However, after adjusting for birthweight and adult BMI, the direct causal relationship between childhood BMI and MASLD disappeared.
Conclusion: For the first time, this MR elucidated new evidence for the effect of life course adiposity on MASLD risk, providing lower birthweight and duration of obesity are independent risk factors for MASLD. Our findings indicated that weight management during distinct time periods plays a significant role in the prevention and treatment of MASLD.
期刊介绍:
BMC Gastroenterology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of gastrointestinal and hepatobiliary disorders, as well as related molecular genetics, pathophysiology, and epidemiology.