Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.
Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.
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DOI：
10.1038/s41467-022-29932-y
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发表时间：
2022-04-28
影响因子：
16.6
通讯作者：
Smith, George Davey
中科院分区：
文献类型：
--
作者：
Richardson, Tom G.;Crouch, Daniel J. M.;Power, Grace M.;Morales-Berstein, Fernanda;Hazelwood, Emma;Fang, Si;Cho, Yoonsu;Inshaw, Jamie R. J.;Robertson, Catherine C.;Sidore, Carlo;Cucca, Francesco;Rich, Steven S.;Todd, John A.;Smith, George Davey
儿童肥胖率的上升被认为是1型糖尿病(T1D)患者发病率上升的原因。在这项研究中，我们使用孟德尔随机化(MR)来提供证据，证明儿童时期的体型对T1D风险有影响(OR = 为2.05每改变体型类别，95%CI = 1.20至3.5，P = 0.008)，在使用多变量MR(OR = 2.32，95%CI = 1.21至4.42，P = 0.013)考虑出生时和成年期的体型后，这种影响仍然存在。我们使用基于n个 = 15,573例和n个 = 158,408个对照(OR = 1.94，95%CI = 1.21至3.12，P = 0.006)的大规模T1D荟萃分析的数据来验证儿童身体大小的这种直接影响。我们还提供了儿童体型影响哮喘、湿疹和甲状腺功能减退症风险的证据，尽管多变量MR表明这些影响是由晚年的体型调节的。我们的发现支持儿童时期较大的体型对被诊断为T1D的风险的因果作用，而其对其他免疫相关疾病的影响可能是通过在生命过程中多年保持超重的长期影响来解释的。1型糖尿病的增加被认为与儿童肥胖症的增加有关，但这种关系还没有被很好地理解。在这项研究中，作者利用孟德尔随机化方法分离了儿童体型对1型糖尿病风险和其他7种免疫相关疾病结果的直接和间接影响。
The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.20 to 3.50, P = 0.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR = 2.32, 95% CI = 1.21 to 4.42, P = 0.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n = 15,573 cases and n = 158,408 controls (OR = 1.94, 95% CI = 1.21 to 3.12, P = 0.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse. The rise in type 1 diabetes is thought to be related to increased childhood obesity, but this relationship is not well understood. In this study, the authors utilize Mendelian randomization to separate the direct and indirect effects of childhood body size on risk of type 1 diabetes and 7 other immune-associated disease outcomes.
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影响因子：
16.2
作者：
Chiang JL;Maahs DM;Garvey KC;Hood KK;Laffel LM;Weinzimer SA;Wolfsdorf JI;Schatz D
通讯作者：
Schatz D
影响因子：
4.4
作者：
Byberg KK;Eide GE;Forman MR;Júlíusson PB;Øymar K
通讯作者：
Øymar K
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
3.5
作者：
Brandkvist M;Bjørngaard JH;Ødegård RA;Åsvold BO;Smith GD;Brumpton B;Hveem K;Richardson TG;Vie GÅ
通讯作者：
Vie GÅ
影响因子：
30.8
作者：
Dooley J;Tian L;Schonefeldt S;Delghingaro-Augusto V;Garcia-Perez JE;Pasciuto E;Di Marino D;Carr EJ;Oskolkov N;Lyssenko V;Franckaert D;Lagou V;Overbergh L;Vandenbussche J;Allemeersch J;Chabot-Roy G;Dahlstrom JE;Laybutt DR;Petrovsky N;Socha L;Gevaert K;Jetten AM;Lambrechts D;Linterman MA;Goodnow CC;Nolan CJ;Lesage S;Schlenner SM;Liston A
通讯作者：
Liston A