Association between systemic lupus erythematosus and inflammatory bowel disease in European and East Asian populations: a two-sample Mendelian randomization study.

Background: Previous studies have shown a coexistence phenomenon between systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), but the causal relationship between them is still unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis using publicly available summary statistics data to evaluate whether there was a causal relationship between the two diseases. Methods: Summary statistics for SLE and IBD were downloaded from the Open Genome-Wide Association Study and the International Inflammatory Bowel Disease Genetics Consortium. European and East Asian populations were included in this MR work. We adopted a series of methods to select instrumental variables that are closely related to SLE and IBD. To make the conclusion more reliable, we applied a variety of different analysis methods, among which the inverse variance-weighted (IVW) method was the main method. In addition, heterogeneity, pleiotropy, and sensitivity were assessed to make the conclusions more convincing. Results: In the European population, a negative causal relationship was observed between SLE and overall IBD (OR = 0.94; 95% CI = 0.90, 0.98; P < 0.004) and ulcerative colitis (UC) (OR = 0.93; 95% CI = 0.88, 0.98; P = 0.006). After removing outliers with Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), the results remained consistent with IVW. However, there was no causal relationship between SLE and Crohn's disease. In the East Asian population, no causal relationship was found between SLE and IBD. Conclusion: Our results found that genetic susceptibility to SLE was associated with lower overall IBD risk and UC risk in European populations. In contrast, no association between SLE and IBD was found in East Asian populations. This work might enrich the previous research results, and it may provide some references for research in the future.

Enhanced weathering input from South Asia to the Indian Ocean since the late Eocene.

Enhanced silicate weathering induced by the uplift of the Himalayan-Tibetan Plateau (HTP) has been considered as the major cause of pCO2 decline and Cenozoic cooling. However, this hypothesis remains to be validated, largely due to the lack of a reliable reconstruction of the HTP weathering flux. Here, we present a 37-million-year record of the difference in the seawater radiogenic neodymium isotopic composition (ΔεNd) of Ocean Drilling Program (ODP) sites and Fe-Mn crusts between the northern and central Indian Ocean, which indicates the contribution of regional weathering input from the South Asian continent to the Indian Ocean. The results show a long-term increase in ΔεNd and thus provide the first critical evidence of enhanced South Asian weathering input since the late Eocene. The evolution coincided well with major pulses of surface uplift in the HTP and global climatic transitions. Our foraminiferal εNd record suggests that tectonic uplift and silicate weathering in South Asia, especially in the Himalayas, might have played a significant role in the late Cenozoic cooling.