Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

/pdf/biological-insights-from-108-schizophrenia-associated-3rfvth8dm9.pdf

Biological insights from 108 schizophrenia-associated genetic loci

For most human complex diseases and traits, SNPs identified by genome-wide association studies (GWAS) explain only a small fraction of the heritability. Here we report a user-friendly software tool called genome-wide complex trait analysis (GCTA), which was developed based on a method we recently developed to address the “missing heritability” problem. GCTA estimates the variance explained by all the SNPs on a chromosome or on the whole genome for a complex trait rather than testing the association of any particular SNP to the trait. We introduce GCTA's five main functions: data management, estimation of the genetic relationships from SNPs, mixed linear model analysis of variance explained by the SNPs, estimation of the linkage disequilibrium structure, and GWAS simulation. We focus on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation. The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets.

https://www.cell.com/ajhg/pdf/S0002-9297(10)00598-7.pdf

GCTA: a tool for genome-wide complex trait analysis.

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...

Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association

Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2); 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m(2); 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative beta-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative beta-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of beta-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that beta-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased beta-cell apoptosis. Since the major defect leading to a decrease in beta-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and beta-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.

https://diabetes.diabetesjournals.org/content/diabetes/52/1/102.full.pdf

β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes

Dental abnormalities in children of fathers with substance use disorders.

Background The degree to which children experience unmet need for dental care during the COVID-19 pandemic and its association with pandemic-related household job or income loss are unknown Methods The authors performed a cross-sectional household survey of 348 families in Pittsburgh, Pennsylvania, from June 25 through July 2, 2020 Unmet need for child dental care and pandemic-related household job or income loss were assessed using caregiver self-report Results Caregivers reported that the greatest unmet child health care need during the COVID-19 pandemic was dental care (16%), followed by medical care for a well visit or vaccination (5%) Approximately 40% of caregivers reported job loss or a decrease in household income due to the COVID-19 pandemic The authors found a significant association between the probability of unmet child dental care and pandemic-related household job or income loss (P = 022) Losing a job or experiencing a decrease in income due to the COVID-19 pandemic was associated with unmet child dental care (relative risk, 177; 95% confidence interval, 108 to 288) Conclusions In this sample, 3 times as many households reported unmet dental care for a child compared with unmet medical care Unmet child dental care was more common in households where pandemic-related job or income loss occurred Practical Implications If unmet dental care continues as a result of the COVID-19 pandemic, nontraditional strategies for delivering dental care can be considered to improve access to dental care for children, such as teledentistry and oral health prevention services in primary care settings

What is the association between income loss during the COVID-19 pandemic and children's dental care?

Purpose: The purpose of this study was to examine whether perceived social support among mothers with high levels of dental caries was associated with their children experiencing high levels of dental caries. Methods: In West Virginia and Pennsylvania from 2002 to 2009, mothers were interviewed and clinical exams were conducted on their one- to six-year-old children. Two hundred and fifty mother-child dyads were analyzed where the mother had high dental caries. Mothers reported perceived social support across four domains (appraisal, tangible, self-esteem, belonging) from the Interpersonal Support Evaluation List instrument (ISEL), with higher scores representing greater support. The association between each social support domain and the probability of high child dental caries was examined. Results: Twenty-seven percent of children (67 out of 250) had high dental caries, and the odds of children having high caries was lower by seven percent for every one point increase in the ISEL appraisal score (odds ratio equals 0.93; 95 percent confidence interval equals 0.88, 0.99). Tangible, self-esteem, and belonging social support ISEL subscales were not significantly associated with high child dental caries (P>0.05). Conclusions: Among mothers with high dental caries, there was modest evidence that appraisal support-the perceived availability of someone to talk to about problems-was associated with lower odds of their children having high dental caries. (Pediatr Dent 2019;41(3):200-5) Received December 2, 2018 | Last Revision April 19, 2019 | Accepted April 22, 2019.

Mother's Perceived Social Support and Children's Dental Caries in Northern Appalachia.

For careful consideration: the reporting of health economic evaluations in dentistry

Background Mothers play a primary role in the health of their children. This role may be of particular importance for children in Appalachia who have increased caries relative to children in other regions of the United States. The authors examined the degree to which a child’s caries experience was in concordance with the mother’s perception of the health of her child’s teeth, and how concordance varied by sociodemographic factors. Methods The authors obtained cross-sectional data on mother-child dyads with children younger than 6 years through the Center for Oral Health Research in Appalachia study. They interviewed and clinically examined a community-based sample of 815 mother-child dyads from Pennsylvania and West Virginia. They used an unadjusted zero-inflated negative binomial model to estimate the association between a mother’s perception of her child’s oral health status and her child’s caries. The authors compared sociodemographic factors between concordant and nonconcordant mother-child dyads using χ2 tests. Results The mother’s perception of her child’s oral health status was associated with the child’s caries experience (P Conclusions and Practical Implications On average, mothers accurately perceived their child’s caries experience. This accuracy was higher for younger children and children with dental insurance. The mother’s awareness of her child’s oral health status could be used to develop effective prevention and treatment strategies, particularly for young children vulnerable to caries.

Robert J. Weyant

Papers

Dental abnormalities in children of fathers with substance use disorders.

What is the association between income loss during the COVID-19 pandemic and children's dental care?

Mother's Perceived Social Support and Children's Dental Caries in Northern Appalachia.

For careful consideration: the reporting of health economic evaluations in dentistry

Association between a child's caries experience and the mother's perception of her child's oral health status.