Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Anesthesia and cor triatriatum

Aims and Objectives: Cor triatriatum sinistrum (CTS) and cor triatriatum dextrum (CTD) are rare congenital anomalies characterized by the presence of a perforated septum which divides the respective atrium into a proximal and distal chamber. This report reviews the perioperative course of patients with uncorrected cor triatriatum (CT) undergoing procedures requiring anesthesia. In addition, we performed a literature search that examines the experience of others regarding the peri-operative course of patients with CT. Materials and Methods: A computerized search of a medical record database was conducted to identify patients with a clinical diagnosis of uncorrected CTD and CTS undergoing surgical procedures. Descriptive statistics were used. Results: We identified 12 adult patients with asymptomatic CTS (n = 7) and CTD (n = 5) who underwent 23 anesthetics. There were no perioperative complications which could be attributed directly to the anatomy of CT. Conclusions: Our observation and review of the literature suggest that patients with asymptomatic CT typically tolerate anesthesia and surgical procedures well

Hemodynamic course during ablation and selective hepatic artery embolization for metastatic liver carcinoid: a retrospective observational study

Background: Manipulation of carcinoid tumors during ablation or selective hepatic artery embolization (transarterial embolization, TAE) can release vasoactive mediators inducing hemodynamic instability. The main aim of our study was to review hemodynamics and complications related to minimally invasive treatments of liver carcinoids with TAE or ablation. Methods: Electronic medical records of all patients with metastatic liver carcinoid undergoing ablation or TAE from 2003 to 2019 were abstracted. Noted were severe hypotension (mean arterial pressure [MAP] ..± 55.ßmmHg), severe hypertension (systolic blood pressure ... 180.ßmmHg), and perioperative complications. Associations of procedure type and pre-procedure octreotide use with intraprocedural hemodynamics were assessed using linear regression. A robust covariance approach using generalized estimating equation method was used to account for multiple observations. Results: A total of 161 patients underwent 98 ablations and 207 TAEs. Severe hypertension was observed in 24 (24.5%) vs. 15 (7.3%), severe hypotension in 56 (57.1%) vs. 6 (2.9%), and cutaneous flushing observed in 2 (2.0%) vs. 48 (23.2%) ablations and TAEs, respectively. After adjusting for preprocedural MAP, ablation was associated with lower intraprocedural MAP compared to TAE (estimate -27.ßmmHg, 95%CI -30 to -24.ßmmHg, p.ß<.ß0.001). Intraprocedural declines in MAP were not affected by preprocedural use of octreotide (p.ß=.ß0.7 for TAE and p.ß=.ß0.4 for ablation). Conclusions: Ablation of liver carcinoids was associated with substantial hemodynamic instability, especially hypotension. In contrast, a higher number of TAE patients had cutaneous flushing. Preprocedural use of octreotide was not associated with attenuation of intraprocedural hypotension

The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. I. An Autosomal Genome Scan for Genes That Predispose to Type 2 Diabetes

We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes