The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.

By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.

SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07–1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06–1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04–1.18, p = 1.84 × 10−3).

We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

The strategies of repair of tetralogy of Fallot change with the age of patients. In children older than 4 years and adults, the optimal strategy may be to use different method of reconstruction of the right ventricular outflow tract from those followed in younger children, so as to avoid, or reduce, the pulmonary insufficiency that is increasingly known to compromise right ventricular function.

From April, 2001, through May, 2008, we undertook complete repair in 312 patients, 180 male and 132 female, with a mean age of 11.3 years ±0.4 years, and a range from 4 to 48 years, with typical clinical and morphological features of tetralogy of Fallot, including 42 patients with the ventriculo-arterial connection of double outlet right ventricle. The operation was performed under moderate hypothermia using blood cardioplegia. The ventricular septal defect was closed with a Dacron patch. When it was considered necessary to resect the musculature within the right ventricular outflow tract, or perform pulmonary valvotomy, we sought to preserve the function of the pulmonary valve by protecting as far as possible the native leaflets, or creating a folded monocusp of autologous pericardium.

The repair was achieved completely through right atrium in 192, through the right ventricular outflow tract in 83, and through the right atrium, the outflow tract, and the pulmonary trunk in 36 patients. A transjunctional patch was inserted in 169 patients, non-valved in all but 9. There were no differences regarding the periods of aortic cross-clamping or cardiopulmonary bypass. Of the patients, 5 died (1.6%), with no influence noted for the transjunctional patch. Of those having a non-valved patch inserted, three-tenths had pulmonary regurgitation of various degree, while those having a valved patch had minimal pulmonary insufficiency and good right ventricular function postoperatively, this being maintained after follow-up of 8 to 24-months.

Based on our experience, we suggest that the current strategy of repair of tetralogy of Fallot in older children and adults should be based on minimizing the insertion of transjunctional patches, this being indicated only in those with very small ventriculo-pulmonary junctions. If such a patch is necessary, then steps should be taken to preserve the function of the pulmonary valve.