Hostname: page-component-7479d7b7d-fwgfc Total loading time: 0 Render date: 2024-07-11T10:36:32.889Z Has data issue: false hasContentIssue false
  • English
  • Français

Assessing the causal relationship of birth weight and childhood obesity on osteoarthritis: a Mendelian randomization study

Published online by Cambridge University Press:  03 June 2024

Zengfeng Xin ,
Lingxiao Xu Open the ORCID record for Lingxiao Xu [Opens in a new window]  and
Lingling Sun
Zengfeng Xin
Affiliation:
Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Orthopedics Research Institute of Zhejiang University, Hangzhou, China Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
Lingxiao Xu
Affiliation:
Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Orthopedics Research Institute of Zhejiang University, Hangzhou, China Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
Lingling Sun*
Affiliation:
Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Orthopedics Research Institute of Zhejiang University, Hangzhou, China Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, China
*
Corresponding author: L. Sun; Email: sunlingling@zju.edu.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

Obesity is associated with osteoarthritis (OA), but few studies have used fetal origin to explore the association. Our study aims to disentangle the causality between birth weight, childhood obesity, and adult OA using Mendelian randomization (MR). We identified single nucleotide polymorphisms (SNPs) related to birth weight (n = 298,142) and childhood obesity (n = 24,160) from two genome-wide association studies contributed by the Early Growth Genetics Consortium. Summary statistics of OA and its phenotypes (knee, hip, spine, hand, thumb, and finger OA) from the Genetics of Osteoarthritis Consortium (n = 826,690) were used to estimate the effects of SNPs on OA. Multivariable MR (MVMR) was conducted to investigate the independent effects of exposures. It turned out that genetically predicted standard deviation increase in birth weight was not associated with OA. In contrast, there was a marginally positive effect of childhood obesity on total [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.00, 1.15 using IVW], knee (OR = 1.13, 95% CI = 1.05, 1.22 using weighted median), hip (OR = 1.13, 95% CI = 1.04, 1.24 using IVW), and spine OA (OR = 1.12, 95% CI = 1.03, 1.22 using IVW), but not hand, thumb, or finger OA. MVMR indicated a potential adulthood body mass index-dependent causal pathway between childhood obesity and OA. In conclusion, no association of birth weight with OA was suggested. Childhood obesity, however, showed a causality with OA in weight-bearing joints, which seems to be a general association of obesity with OA.

Keywords

Birth weightChildhood obesityOsteoarthritisMendelian randomization
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 15 , 2024 , e12
Check for updates
Copyright
© The Author(s), 2024. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Zengfeng Xin and Lingxiao Xu contributed equally to this work and co-first authors.

References

Peat, G, Thomas, MJ. Osteoarthritis year in review 2020: epidemiology & therapy. Osteoarthr Cartilage. 2021; 29(2), 180–189.CrossRefGoogle ScholarPubMed
World HO. World Heath Organization. 2021; Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed June 3, 2023.Google Scholar
Litwic, A, Edwards, MH, Dennison, EM, Cooper, C. Epidemiology and burden of osteoarthritis. Brit Med Bull. 2013; 105(1), 185–199.CrossRefGoogle ScholarPubMed
Reyes, C, Leyland, KM, Peat, G, Cooper, C, Arden, NK, Prieto-Alhambra, D. Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and hand osteoarthritis: a population-based cohort study. Arthritis Rheumatol. 2016; 68(8), 1869–1875.CrossRefGoogle ScholarPubMed
Blagojevic, M, Jinks, C, Jeffery, A, Jordan, KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthr Cartilage. 2010; 18(1), 24–33.CrossRefGoogle ScholarPubMed
Antony, B, Jones, G, Venn, A, et al. Association between childhood overweight measures and adulthood knee pain, stiffness and dysfunction: a 25-year cohort study. Ann Rheum Dis. 2015; 74(4), 711–717.CrossRefGoogle ScholarPubMed
Molina-Garcia, P, Migueles, JH, Cadenas-Sanchez, C, et al. A systematic review on biomechanical characteristics of walking in children and adolescents with overweight/obesity:Possible implications for the development of musculoskeletal disorders. Obes Rev. 2019; 20(7), 1033–1044.CrossRefGoogle ScholarPubMed
Poole, J, Sayer, AA, Cox, V, et al. Birth weight, osteoarthritis of the hand, and cardiovascular disease in men. Ann Rheum Dis. 2003; 62(10), 1029–1029.CrossRefGoogle ScholarPubMed
Hussain, SM, Wang, Y, Wluka, AE, et al. Association of low birth weight and preterm birth with the incidence of knee and hip arthroplasty for osteoarthritis. Arthrit Care Res. 2015; 67(4), 502–508.CrossRefGoogle ScholarPubMed
Hussain, SM, Ackerman, IN, Wang, Y, Zomer, E, Cicuttini, FM. Could low birth weight and preterm birth be associated with significant burden of hip osteoarthritis? A systematic review. Arthritis Res Ther. 2018; 20(1), 121.CrossRefGoogle ScholarPubMed
Barker, DJ. The fetal and infant origins of adult disease. BMJ (Clinical research ed). 1990; 301(6761), 1111.CrossRefGoogle ScholarPubMed
Lucas, A, Fewtrell, MS, Cole, TJ. Fetal origins of adult disease-the hypothesis revisited. BMJ (Clinical research ed). 1999; 319(7204), 245–249.CrossRefGoogle ScholarPubMed
Antoniades, L, MacGregor, AJ, Andrew, T, Spector, TD. Association of birth weight with osteoporosis and osteoarthritis in adult twins. Rheumatology (Oxford, England). 2003; 42(6), 791–796.CrossRefGoogle ScholarPubMed
Wills, AK, Black, S, Cooper, R, et al. Life course body mass index and risk of knee osteoarthritis at the age of 53 years: evidence from the 1946 British birth cohort study. Ann Rheum Dis. 2012; 71(5), 655–660.CrossRefGoogle ScholarPubMed
Emdin, CA, Khera, AV, Kathiresan, S. Mendelian randomization. JAMA. 2017; 318(19), 1925–1926.CrossRefGoogle ScholarPubMed
Davey Smith, G, Hemani, G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014; 23(1), R89–98.CrossRefGoogle ScholarPubMed
Davies, NM, Holmes, MV, Davey Smith, G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Bradfield, JP, Vogelezang, S, Felix, JF, et al. A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity. Hum Mol Genet. 2019; 28(19), 3327–3338.CrossRefGoogle ScholarPubMed
Boer, CG, Hatzikotoulas, K, Southam, L, et al. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. 2021; 184(18), 4784–4818.e17.CrossRefGoogle ScholarPubMed
Hemani, G, Zheng, J, Elsworth, B, et al. The MR-base platform supports systematic causal inference across the human phenome. eLife. 2018; 7, 34408.CrossRefGoogle ScholarPubMed
Burgess, S, Bowden, J, Fall, T, Ingelsson, E, Thompson, SG. Sensitivity analyses for robust Causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology (Cambridge, Mass). 2017; 28(1), 30–42.CrossRefGoogle ScholarPubMed
Bowden, J, Davey Smith, G, Haycock, PC, Burgess, S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016; 40(4), 304–314.CrossRefGoogle ScholarPubMed
Bowden, J, Davey Smith, G, Burgess, S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015; 44(2), 512–525.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Yengo, L, Sidorenko, J, Kemper, KE, et al. Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum Mol Genet. 2018; 27(20), 3641–3649.CrossRefGoogle ScholarPubMed
Yavorska, OO, Burgess, S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017; 46(6), 1734–1739.CrossRefGoogle Scholar
Rees, JMB, Wood, AM, Burgess, S. Extending the MR-Egger method for multivariable Mendelian randomization to correct for both measured and unmeasured pleiotropy. Stat Med. 2017; 36(29), 4705–4718.CrossRefGoogle ScholarPubMed
Burgess, S, Thompson, SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015; 181(4), 251–260.CrossRefGoogle ScholarPubMed
Jordan, KM, Syddall, H, Dennison, EM, Cooper, C, Arden, NK. Birthweight, vitamin D receptor gene polymorphism, and risk of lumbar spine osteoarthritis. The Journal of rheumatology. 2005; 32(4), 678–683.Google ScholarPubMed
Clynes, MA, Parsons, C, Edwards, MH, et al. Further evidence of the developmental origins of osteoarthritis: results from the hertfordshire cohort study. J Dev Orig Hlth Dis. 2014; 5(6), 453–458.CrossRefGoogle ScholarPubMed
Zengini, E, Hatzikotoulas, K, Tachmazidou, I, et al. Genome-wide analyses using UK biobank data provide insights into the genetic architecture of osteoarthritis. Nat Genet. 2018; 50(4), 549–558.CrossRefGoogle ScholarPubMed
Widhalm, HK, Seemann, R, Hamboeck, M, et al. Osteoarthritis in morbidly obese children and adolescents, an age-matched controlled study. Knee Surg Sports Traumatol Arthrosc. 2016; 24(3), 644–652.CrossRefGoogle ScholarPubMed
Wabitsch, M, Horn, M, Esch, U, et al. Silent slipped capital femoral epiphysis in overweight and obese children and adolescents. Eur J Pediatr. 2012; 171(10), 1461–1465.CrossRefGoogle ScholarPubMed
Walker, JL, Hosseinzadeh, P, White, H, et al. Idiopathic Genu Valgum and its association with obesity in children and adolescents. J Pediatr Orthoped. 2019; 39(7), 347–352.CrossRefGoogle ScholarPubMed
Sayer, AA, Poole, J, Cox, V, et al. Weight from birth to 53 years: a longitudinal study of the influence on clinical hand osteoarthritis. Arthritis Rheum. 2003; 48(4), 1030–1033.CrossRefGoogle Scholar
Sokolove, J, Lepus, CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskel Dis. 2013; 5(2), 77–94.CrossRefGoogle Scholar
Malemud, CJ. Biologic basis of osteoarthritis: state of the evidence. Curr Opin Rheumatol. 2015; 27(3), 289–294.CrossRefGoogle ScholarPubMed
Berenbaum, F, Eymard, F, Houard, X. Osteoarthritis, inflammation and obesity. Curr Opin Rheumatol. 2013; 25(1), 114–118.CrossRefGoogle ScholarPubMed
Funck-Brentano, T, Nethander, M, Movérare-Skrtic, S, Richette, P, Ohlsson, C. Causal factors for knee, hip, and hand osteoarthritis: a mendelian randomization study in the UK biobank. Arthritis Rheumatol. 2019; 71(10), 1634–1641.CrossRefGoogle ScholarPubMed
Cao, Z, Wu, Y, Li, Q, Li, Y, Wu, J. A causal relationship between childhood obesity and risk of osteoarthritis: results from a two-sample Mendelian randomization analysis. Ann Med. 2022; 54(1), 1636–1645.CrossRefGoogle ScholarPubMed
Supplementary material: File

Xin et al. supplementary material

Xin et al. supplementary material
Download Xin et al. supplementary material(File)
File 121.2 KB