A genome-wide association study of social trust in 33,882 Danish blood donors.

Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it.

Deep integrative models for large-scale human genomics.

Polygenic risk scores (PRSs) are expected to play a critical role in precision medicine. Currently, PRS predictors are generally based on linear models using summary statistics, and more recently individual-level data. However, these predictors mainly capture additive relationships and are limited in data modalities they can use. We developed a deep learning framework (EIR) for PRS prediction which includes a model, genome-local-net (GLN), specifically designed for large-scale genomics data. The framework supports multi-task learning, automatic integration of other clinical and biochemical data, and model explainability. When applied to individual-level data from the UK Biobank, the GLN model demonstrated a competitive performance compared to established neural network architectures, particularly for certain traits, showcasing its potential in modeling complex genetic relationships. Furthermore, the GLN model outperformed linear PRS methods for Type 1 Diabetes, likely due to modeling non-additive genetic effects and epistasis. This was supported by our identification of widespread non-additive genetic effects and epistasis in the context of T1D. Finally, we constructed PRS models that integrated genotype, blood, urine, and anthropometric data and found that this improved performance for 93% of the 290 diseases and disorders considered. EIR is available at https://github.com/arnor-sigurdsson/EIR.

Perioperative Complications of Cesarean Delivery Myomectomy: A Meta-analysis.

OBJECTIVE: To assess the association of myomectomy during cesarean delivery with intraoperative and perioperative maternal morbidity. DATA SOURCES: We searched MEDLINE (1966-2017), Scopus (2004-2017), ClinicalTrials.gov (2008-2017), EMBASE (1980-2017), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases. METHODS OF STUDY SELECTION: We selected all observational studies that reported outcomes on patients undergoing myomectomy at the time of cesarean delivery. Statistical meta-analysis was performed with RevMan 5.3. RESULTS: Nineteen studies were included in our systematic review with a total number of 3,900 women. Among them, 2,301 women had myomectomy during cesarean delivery and 1,599 had cesarean delivery only. Women undergoing concomitant myomectomy had a mild decline in hemoglobin compared with those who had cesarean delivery only (mean difference 0.25 mg/dL, 95% CI 0.06-0.45). Myomectomy at the time of cesarean delivery is associated with longer surgical time compared with cesarean delivery alone (mean difference 13.87 minutes, 95% CI 4.78-22.95). Blood transfusion (odds ratio [OR] 1.41, 95% CI 0.96-2.07) and postoperative fever (OR 1.12, 95% CI 0.80-1.56) rates did not differ between the two groups (myomectomy compared with no myomectomy). A statistically, but not clinically, significant increase in postoperative hospitalization was evident in the myomectomy group (mean difference 0.35 days, 95% CI 0.25-0.46). CONCLUSION: This systematic review and meta-analysis of observational studies demonstrated an association with increased operative time and hemoglobin drop in patients who underwent cesarean myomectomy compared with cesarean delivery alone. No increased rate of major hemorrhage or need for transfusion was identified. Cesarean myomectomy may be considered in cases of isolated myomas, although randomized trials are needed.