Affiliation:
1. Department of Epidemiology and Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
2. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
3. Department of Pediatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Abstract
Abstract
Observational studies showed an inverse association between birth weight and chronic kidney disease (CKD) in adulthood existed. However, whether such an association is causal remains fully elusive. Moreover, none of prior studies distinguished the direct fetal effect from the indirect maternal effect. Herein, we aimed to investigate the causal relationship between birth weight and CKD and to understand the relative fetal and maternal contributions. Meta-analysis (n = ~22 million) showed that low birth weight led to ~83% (95% confidence interval [CI] 37–146%) higher risk of CKD in late life. With summary statistics from large scale GWASs (n = ~300 000 for birth weight and ~481 000 for CKD), linkage disequilibrium score regression demonstrated birth weight had a negative maternal, but not fetal, genetic correlation with CKD and several other kidney-function related phenotypes. Furthermore, with multiple instruments of birth weight, Mendelian randomization showed there existed a negative fetal casual association (OR = 1.10, 95% CI 1.01–1.16) between birth weight and CKD; a negative but non-significant maternal casual association (OR = 1.09, 95% CI 0.98–1.21) was also identified. Those associations were robust against various sensitivity analyses. However, no maternal/fetal casual effects of birth weight were significant for other kidney-function related phenotypes. Overall, our study confirmed the inverse association between birth weight and CKD observed in prior studies, and further revealed the shared maternal genetic foundation between low birth weight and CKD, and the direct fetal and indirect maternal causal effects of birth weight may commonly drive this negative relationship.
Funder
National Natural Science Foundation of China
National Natural Science Foundation of Jiangsu
Natural Science Foundation of Shandong Province
Young Scholars Program of Shandong University
Youth Foundation of Humanity and Social Science
Ministry of Education of China
China Postdoctoral Science Foundation
Postdoctoral Science Foundation of Xuzhou Medical University
National Bureau of Statistics of China
Postgraduate Research & Practice Innovation Program of Jiangsu Province
Priority Academic Program Development of Jiangsu Higher Education Institutions
Publisher
Oxford University Press (OUP)
Subject
Genetics (clinical),Genetics,Molecular Biology,General Medicine
Cited by
18 articles.
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