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.

Prior studies have shown that there is an inverse association between birth weight and stroke in adulthood; however, whether such association is causal remains yet known and those studies cannot distinguish between the direct fetal effect and the indirect maternal effect. The aim of the study is to untangle such relationship using novel statistical genetic approaches.

BackgroundIn two-sample Mendelian randomization (MR) studies, sex instrumental heterogeneity is an important problem needed to address carefully, which however is often overlooked and may lead to misleading causal inference.MethodsWe first employed cross-trait linkage disequilibrium score regression (LDSC), Pearson’s correlation analysis, and the Cochran’s Q test to examine sex genetic similarity and heterogeneity in instrumental variables (IVs) of exposures. Simulation was further performed to explore the influence of sex instrumental heterogeneity on causal effect estimation in sex-specific two-sample MR analyses. Furthermore, we chose breast/prostate cancer as outcome and four anthropometric traits as exposures as an illustrative example to illustrate the importance of taking sex heterogeneity of instruments into account in MR studies.ResultsThe simulation definitively demonstrated that sex-combined IVs can lead to biased causal effect estimates in sex-specific two-sample MR studies. In our real applications, both LDSC and Pearson’s correlation analyses showed high genetic correlation between sex-combined and sex-specific IVs of the four anthropometric traits, while nearly all the correlation coefficients were larger than zero but less than one. The Cochran’s Q test also displayed sex heterogeneity for some instruments. When applying sex-specific instruments, significant discrepancies in the magnitude of estimated causal effects were detected for body mass index (BMI) on breast cancer (P = 1.63E-6), for hip circumference (HIP) on breast cancer (P = 1.25E-20), and for waist circumference (WC) on prostate cancer (P = 0.007) compared with those generated with sex-combined instruments.ConclusionOur study reveals that the sex instrumental heterogeneity has non-ignorable impact on sex-specific two-sample MR studies and the causal effects of anthropometric traits on breast/prostate cancer would be biased if sex-combined IVs are incorrectly employed.

The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease in which pathogenic autoantibodies and immune complexes are formed and mediate multiple organ and tissue damage. Thrombosis is one of the most common causes of death in patients with SLE. Anticoagulant therapy blocks the vicious cycle between inflammation and thrombosis, which may greatly improve the long-term prognosis of patients with SLE. However, the etiology and pathogenesis of this disease are very complicated and have not yet been fully clarified. Therefore, in the present review, we will highlight the characteristics and mechanisms of thrombosis and focus on the anticoagulant drugs commonly used in clinical practice, thus, providing a theoretical basis for scientific and reasonable anticoagulant therapy in clinical practice.