The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

An integrated expression atlas of miRNAs and their promoters in human and mouse

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Individual Differences in Thresholds and Consumer Preferences for Rotundone Added to Red Wine

Rotundone is an aromatic compound found in the skin of some grapes (e.g., Shiraz, Noiret) that contributes peppery notes to wines made with these varieties. There may be a specific anosmia for rotundone, as some individuals are unable to detect it even at high concentrations, despite otherwise normal olfaction. This may affect perception of and preference for rotundone-containing wines. Here, we report rotundone detection thresholds (orthonasal n = 56; retronasal n = 53) and rejection thresholds (n = 86) in red wine for a convenience sample of non-expert consumers in Pennsylvania. Focus groups were conducted to better understand consumer attitudes and preferences for rotundone. Ortho- and retronasal detection thresholds were nearly identical (140 v. 146 ng/L). Roughly 40% of our sample was anosmic to rotundone, extending evidence for a specific anosmia to a North American cohort. As ortho- and retronasal thresholds were extremely similar, future work on rotundone can rely on orthonasal assessment. In our participants, added rotundone was generally disliked, and in focus groups, the concept of a &lsquo;peppery&rsquo; wine was not appealing. Winemakers need to carefully consider biological and attitudinal segmentation when making and marketing peppery wines. Further work is needed to identify the genetic basis for this anosmia

Minimally Invasive Hysterectomy for Uteri Greater Than One Kilogram.

Background and objectivesTo assess the feasibility and safety of minimally invasive hysterectomy for uteri &gt;1 kg.MethodsClinical and surgical characteristics were collected for patients in an academic tertiary care hospital. Included were patients who underwent minimally invasive hysterectomy by 1 of 3 fellowship-trained gynecologists from January 1, 2009, to July 1, 2015 and subsequently had confirmed uterine weights of 1 kg or greater on pathology report. Both robotic and conventional laparoscopic procedures were included.ResultsDuring the study period, 95 patients underwent minimally invasive hysterectomy with confirmed uterine weight over 1 kg. Eighty-eight percent were performed with conventional laparoscopy and 12.6% with robot-assisted laparoscopy. The median weight (range) was 1326 g (range, 1000-4800). The median estimated blood loss was 200 mL (range, 50-2000), and median operating time was 191 minutes (range, 75-478). Five cases were converted to laparotomy (5.2%). Four cases were converted secondary to hemorrhage and one secondary to extensive adhesions. There were no conversions after 2011. Intraoperative transfusion was given in 6.3% of cases and postoperative transfusion in 6.3% of cases. However, after 2013, the rate of intraoperative transfusion decreased to 1.0% and postoperative transfusion to 2.1%. Of the 95 cases, there were no cases with malignancy.ConclusionsThis provides the largest case series of hysterectomy over 1 kg completed by a minimally invasive approach. Our complication rate improved with experience and was comparable to other studies of minimally invasive hysterectomy for large uteri. When performed by experienced surgeons, minimally invasive hysterectomy for uteri &gt;1 kg can be considered feasible and safe

Predicting missing biomarker data in a longitudinal study of Alzheimer disease

Objective:To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).Methods:The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.Results:CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.Conclusion:The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD