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Obesity (Silver Spring, Md.)
10, 2023;31 (10): 2603-2614.

Birth weight, childhood obesity, adulthood obesity and body composition, and gastrointestinal diseases: a Mendelian randomization study.

Shuai Yuan, Xixian Ruan, Yuhao Sun, Tian Fu, Jianhui Zhao, Minzi Deng, Jie Chen, Xue Li, Susanna C Larsson
Author Information
  1. Shuai Yuan: Department of Big Data in Health Science, Center of Clinical Big Data and Analytics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. ORCID
  2. Xixian Ruan: Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China. ORCID
  3. Yuhao Sun: Department of Big Data in Health Science, Center of Clinical Big Data and Analytics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  4. Tian Fu: Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China.
  5. Jianhui Zhao: Department of Big Data in Health Science, Center of Clinical Big Data and Analytics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  6. Minzi Deng: Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China.
  7. Jie Chen: Department of Big Data in Health Science, Center of Clinical Big Data and Analytics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. ORCID
  8. Xue Li: Department of Big Data in Health Science, Center of Clinical Big Data and Analytics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  9. Susanna C Larsson: Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. ORCID
PMID: 37664887 DOI: 10.1002/oby.23857

Abstract

OBJECTIVE: This Mendelian randomization study aimed to investigate the associations of birth weight, childhood BMI, and adulthood BMI, waist-hip ratio, and body composition with the risk of 24 gastrointestinal diseases.
METHODS: Independent genetic instruments associated with the exposures at the genome-wide significance level (p < 5 × 10 ) were selected from corresponding large-scale genome-wide association studies. Summary-level data for gastrointestinal diseases were obtained from the UK Biobank, the FinnGen study, and large consortia of European ancestry.
RESULTS: Genetically predicted higher levels of birth weight were associated with a lower risk of gastroesophageal reflux. Genetically predicted higher childhood BMI was associated with an increased risk of duodenal ulcer, nonalcoholic fatty liver disease, and cholelithiasis. However, the associations did not persist after adjusting for genetically predicted adulthood BMI. Genetically predicted higher adulthood BMI and waist-hip ratio were associated with 19 and 17 gastrointestinal diseases, respectively. Genetically predicted greater visceral adiposity was associated with an increased risk of 17 gastrointestinal diseases. There were no strong associations among genetically predicted whole-body fat and fat-free mass indices with gastrointestinal diseases.
CONCLUSIONS: This study suggests that greater adulthood adiposity, measured as either BMI, waist-hip ratio, or visceral adipose tissue, is causally associated with an increased risk of a broad range of gastrointestinal diseases in the European population.

References

  1. Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022;133:155217. doi:10.1016/j.metabol.2022.155217
  2. World Health Organization. WHO European Regional Obesity Report 2022. WHO; 2022.
  3. Peery AF, Crockett SD, Murphy CC, et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018. Gastroenterology. 2019;156(1):254-272.e11.
  4. Peery AF, Crockett SD, Murphy CC, et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2021. Gastroenterology. 2022;162(2):621-644.
  5. Eusebi LH, Ratnakumaran R, Yuan Y, Solaymani-Dodaran M, Bazzoli F, Ford AC. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut. 2018;67(3):430-440.
  6. Pyo JH, Lee H, Kim JE, et al. Obesity and risk of peptic ulcer disease: a large-scale health check-up cohort study. Nutrients. 2019;11(6):1288. doi:10.3390/nu11061288
  7. Peery AF, Keil A, Jicha K, Galanko JA, Sandler RS. Association of obesity with colonic diverticulosis in women. Clin Gastroenterol Hepatol. 2020;18(1):107-114.e1.
  8. Li H, Boakye D, Chen X, et al. Associations of body mass index at different ages with early-onset colorectal cancer. Gastroenterology. 2022;162(4):1088-1097.e3.
  9. Hagstrom H, Tynelius P, Rasmussen F. High BMI in late adolescence predicts future severe liver disease and hepatocellular carcinoma: a national, population-based cohort study in 1.2 million men. Gut. 2018;67(8):1536-1542.
  10. Chan SS, Luben R, Olsen A, et al. Body mass index and the risk for Crohn's disease and ulcerative colitis: data from a European prospective cohort study (the IBD in EPIC study). Am J Gastroenterol. 2013;108(4):575-582.
  11. Khera AV, Chaffin M, Wade KH, et al. Polygenic prediction of weight and obesity trajectories from birth to adulthood. Cell. 2019;177(3):587-596.e9.
  12. Vongsuvanh R, George J, Qiao L, van der Poorten D. Visceral adiposity in gastrointestinal and hepatic carcinogenesis. Cancer Lett. 2013;330(1):1-10.
  13. Fleming CA, O'Connell EP, Kavanagh RG, et al. Body composition, inflammation, and 5-year outcomes in colon cancer. JAMA Netw Open. 2021;4(8):e2115274. doi:10.1001/jamanetworkopen.2021.15274
  14. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23(R1):R89-R98.
  15. Vithayathil M, Carter P, Kar S, Mason AM, Burgess S, Larsson SC. Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: a Mendelian randomisation study. PLoS Med. 2021;18(7):e1003706. doi:10.1371/journal.pmed.1003706
  16. Yuan S, Gill D, Giovannucci EL, Larsson SC. Obesity, type 2 diabetes, lifestyle factors, and risk of gallstone disease: a Mendelian randomization investigation. Clin Gastroenterol Hepatol. 2022;20(3):e529-e537.
  17. Warrington NM, Beaumont RN, Horikoshi M, et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet. 2019;51(5):804-814.
  18. Felix JF, Bradfield JP, Monnereau C, et al. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum Mol Genet. 2016;25(2):389-403.
  19. Pulit SL, Stoneman C, Morris AP, et al. Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry. Hum Mol Genet. 2019;28(1):166-174.
  20. Karlsson T, Rask-Andersen M, Pan G, et al. Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease. Nat Med. 2019;25(9):1390-1395.
  21. Larsson SC, Burgess S. Fat mass and fat-free mass in relation to cardiometabolic diseases: a two-sample Mendelian randomization study. J Intern Med. 2020;288(2):260-262.
  22. Sudlow C, Gallacher J, Allen N, et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3):e1001779. doi:10.1371/journal.pmed.1001779
  23. FinnGen. https://finngen.gitbook.io/documentation/.
  24. Liu JZ, van Sommeren S, Huang H, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47(9):979-986.
  25. Guindo-Martinez M, Amela R, Bonas-Guarch S, et al. The impact of non-additive genetic associations on age-related complex diseases. Nat Commun. 2021;12(1):2436. doi:10.1038/s41467-021-21952-4
  26. Zhou W, Zhao Z, Nielsen JB, et al. Scalable generalized linear mixed model for region-based association tests in large biobanks and cohorts. Nat Genet. 2020;52(6):634-639.
  27. Brion MJ, Shakhbazov K, Visscher PM. Calculating statistical power in Mendelian randomization studies. Int J Epidemiol. 2013;42(5):1497-1501.
  28. Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017;46(6):1734-1739.
  29. Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32(5):377-389.
  30. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693-698.
  31. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359(1):61-73.
  32. Chmurzynska A. Fetal programming: link between early nutrition, DNA methylation, and complex diseases. Nutr Rev. 2010;68(2):87-98.
  33. Feakins RM. Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract. Histopathology. 2016;68(5):630-640.
  34. Kant P, Hull MA. Excess body weight and obesity-the link with gastrointestinal and hepatobiliary cancer. Nat Rev Gastroenterol Hepatol. 2011;8(4):224-238.
  35. Gharahkhani P, Ong JS, An J, et al. Effect of increased body mass index on risk of diagnosis or death from cancer. Br J Cancer. 2019;120(5):565-570.
  36. Langdon RJ, Richmond RC, Hemani G, et al. A phenome-wide Mendelian randomization study of pancreatic cancer using summary genetic data. Cancer Epidemiol Biomarkers Prev. 2019;28(12):2070-2078.
  37. Camilleri M, Malhi H, Acosta A. Gastrointestinal complications of obesity. Gastroenterology. 2017;152(7):1656-1670.
  38. Chiang DJ, McCullough AJ. The impact of obesity and metabolic syndrome on alcoholic liver disease. Clin Liver Dis. 2014;18(1):157-163.
  39. Stampfer MJ, Maclure KM, Colditz GA, Manson JE, Willett WC. Risk of symptomatic gallstones in women with severe obesity. Am J Clin Nutr. 1992;55(3):652-658.
  40. Katuchova J, Bober J, Harbulak P, et al. Obesity as a risk factor for severe acute pancreatitis patients. Wien Klin Wochenschr. 2014;126(7-8):223-227.
  41. Koenen M, Hill MA, Cohen P, Sowers JR. Obesity, adipose tissue and vascular dysfunction. Circ Res. 2021;128(7):951-968.
  42. Emerenziani S, Rescio MP, Guarino MP, Cicala M. Gastro-esophageal reflux disease and obesity, where is the link? World J Gastroenterol. 2013;19(39):6536-6539.
  43. MacInnis RJ, English DR, Hopper JL, Giles GG. Body size and composition and the risk of gastric and oesophageal adenocarcinoma. Int J Cancer. 2006;118(10):2628-2631.
  44. Ma W, Jovani M, Liu PH, et al. Association between obesity and weight change and risk of diverticulitis in women. Gastroenterology. 2018;155(1):58-66.e4.
  45. Ismaiel A, Jaaouani A, Leucuta DC, Popa SL, Dumitrascu DL. The visceral adiposity index in non-alcoholic fatty liver disease and liver fibrosis-systematic review and meta-analysis. Biomedicines. 2021;9(12):1890. doi:10.3390/biomedicines9121890
  46. Schlesinger S, Aleksandrova K, Pischon T, et al. Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort. Int J Cancer. 2013;132(3):645-657.
  47. Bonfrate L, Wang DQ, Garruti G, Portincasa P. Obesity and the risk and prognosis of gallstone disease and pancreatitis. Best Pract Res Clin Gastroenterol. 2014;28(4):623-635.
  48. Sekine K, Nagata N, Sakamoto K, et al. Abdominal visceral fat accumulation measured by computed tomography associated with an increased risk of gallstone disease. J Gastroenterol Hepatol. 2015;30(8):1325-1331.
  49. Aune D, Greenwood DC, Chan DS, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol. 2012;23(4):843-852.
  50. Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract. 2005;69(1):29-35.
  51. Balistreri CR, Caruso C, Candore G. The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediators Inflamm. 2010;2010:802078. doi:10.1155/2010/802078
  52. Crooks B, Stamataki NS, McLaughlin JT. Appetite, the enteroendocrine system, gastrointestinal disease and obesity. Proc Nutr Soc. 2021;80(1):50-58.
  53. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28(1):20-47.
  54. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023.
  55. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761-1772.
  56. Despres JP. Excess visceral adipose tissue/ectopic fat the missing link in the obesity paradox? J Am Coll Cardiol. 2011;57(19):1887-1889.

MeSH Term

Child
Humans
Pediatric Obesity
Birth Weight
Genome-Wide Association Study
Mendelian Randomization Analysis
Gastrointestinal Diseases
Body Composition
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 3

Word Cloud

Created with Highcharts 10.0.0gastrointestinalBMIdiseasesassociatedpredictedadulthoodriskstudyGeneticallyassociationsweightchildhoodwaist-hipratiohigherincreasedMendelianrandomizationbirthbodycompositiongenome-wideEuropeangenetically17greatervisceraladiposityobesityOBJECTIVE:aimedinvestigate24METHODS:Independentgeneticinstrumentsexposuressignificancelevelp < 5 × 10selectedcorrespondinglarge-scaleassociationstudiesSummary-leveldataobtainedUKBiobankFinnGenlargeconsortiaancestryRESULTS:levelslowergastroesophagealrefluxduodenalulcernonalcoholicfattyliverdiseasecholelithiasisHoweverpersistadjusting19respectivelystrongamongwhole-bodyfatfat-freemassindicesCONCLUSIONS:suggestsmeasuredeitheradiposetissuecausallybroadrangepopulationBirthdiseases:

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