Racial/Ethnic Disparities in Psychiatric Traits and Diagnoses within a Community-based Sample of Children and Youth: Disparités raciales/ethniques dans les traits et diagnostics psychiatriques au sein d'un échantillon communautaire d'enfants et de jeunes.

OBJECTIVE: Racial/ethnic disparities in the prevalence of psychiatric disorders have been reported, but have not accounted for the prevalence of the traits that underlie these disorders. Examining rates of diagnoses in relation to traits may yield a clearer understanding of the degree to which racial/ethnic minority youth in Canada differ in their access to care. We sought to examine differences in self/parent-reported rates of diagnoses for obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders after adjusting for differences in trait levels between youth from three racial/ethnic groups: White, South Asian and East Asian. METHOD: We collected parent or self-reported ratings of OCD, ADHD and anxiety traits and diagnoses for 6- to 17-year-olds from a Canadian general population sample (Spit for Science). We examined racial/ethnic differences in trait levels and the odds of reporting a diagnosis using mixed-effects linear models and logistic regression models. RESULTS: East Asian (N = 1301) and South Asian (N = 730) youth reported significantly higher levels of OCD and anxiety traits than White youth (N = 6896). East Asian and South Asian youth had significantly lower odds of reporting a diagnosis for OCD (odds ratio [OR]East Asian = 0.08 [0.02, 0.41]; ORSouth Asian = 0.05 [0.00, 0.81]), ADHD (OREast Asian = 0.27 [0.16, 0.45]; ORSouth Asian = 0.09 [0.03, 0.30]) and anxiety (OREast Asian = 0.21 [0.11, 0.39]; ORSouth Asian = 0.12 [0.05, 0.32]) than White youth after accounting for psychiatric trait levels. CONCLUSIONS: These results suggest a discrepancy between trait levels of OCD, ADHD and anxiety and rates of diagnoses for East Asian and South Asian youth. This discrepancy may be due to increased barriers for ethnically diverse youth to access mental health care. Efforts to understand and mitigate these barriers in Canada are needed.

We know that there is there are differences in the prevalence of childhood mental illnesses by race/ethnic group, which may be related to disproportionate access to mental health care. What is unknown is whether there this difference in prevalence is related to differences in the presence of symptoms for mental illness or whether children and youth from marginalized racial/ethnic groups have symptoms but are not getting diagnosed. This information is needed to understand the degree to which children and youth from marginalized race/ethnicity groups are accessing mental health care in Canada. We tested the differences in reported symptoms and diagnosis of three common and impairing childhood-onset disorders (obsessive-compulsive disorder­OCD), attention-deficit/hyperactivity disorder­ADHD and anxiety disorders) in children and youth (6­17 years of age) living in Canada that were from three racial/ethnic groups: White, South Asian and East Asian. East Asian and South Asian youth reported significantly higher levels of OCD and anxiety traits than White youth. However, East Asian and South Asian youth were significantly less likely than White youth to have a reported diagnosis of OCD, ADHD or anxiety even after accounting for symptom levels for each disorder. Our findings suggest that East and South Asian children are less likely than White children to get a diagnosis for common mental illness even if they have symptoms of that mental illness. This gap in receiving a diagnosis might be because of more barriers to mental health care for children and youth from marginalized racial/ethnic groups but we need more research to pinpoint the cause.

Guideline concordant care for patients with locally advanced cervical cancer by disaggregated Asian American and Native Hawaiian/Pacific Islander groups: A National Cancer Database Analysis.

OBJECTIVE: Despite the within-group heterogeneity, Asian American (AA) and Native Hawaiian and Pacific Islander (NH/PI) patients are often grouped together. We compared the patterns of guideline-concordant care for locally advanced cervical cancer for disaggregated AA and NH/PI patients. METHODS: Patients with stage II-IVA cervical cancer between 2004 and 2020 were identified from the National Cancer Database. AA patients were disaggregated as East Asian (EA), South Asian (SA), and Southeast Asian (SEA). NH/PI patients were classified as a distinct racial subgroup. The primary outcome was the proportion undergoing guideline-concordant care, defined by radiation therapy with concurrent chemotherapy, brachytherapy, and completion of treatment within eight weeks. RESULTS: Of 48,116 patients, 2107 (4%) were AA and 171 (<1%) were NH/PI. Of the AA patients, 36% were SEA, 31% were EA, 12% were SA, and 21% could not be further disaggregated due to missing or unknown data. NH/PI patients were more likely to be diagnosed at an early age (53% NH/PI vs. 30% AA, p < 0.001) and have higher rates of comorbidities (18% NH/PI vs. 14% AA, p < 0.001). Within the AA subgroups, only 82% of SEA patients received concurrent chemotherapy compared to 91% of SA patients (p = 0.026). SA patients had the longest median OS (158 months) within the AA subgroups compared to SEA patients (113 months, p < 0.001). CONCLUSION: Disparities exist in the receipt of standard of care treatment for cervical cancer by racial and ethnic subgroups. It is imperative to disaggregate race and ethnicity data to understand potential differences in care and tailor interventions to achieve health equity.

Culturally and Linguistically Diverse Gamblers of East Asian Descent in Australia: A Comprehensive Review of Current Evidence.

As a country with one of the highest per capita gambling losses per year in the world, and an evolving multicultural profile, Australia has become an important setting in which to examine the harms and benefits related to gambling. The Australian population includes people from East Asian cultural backgrounds who are a key demographic of interest for gambling operators planning to grow revenue. However, Australian gambling research has concentrated primarily on those belonging to the dominant cultural group. Most of the previous and limited number of studies to examine gambling among culturally and linguistically diverse (CALD) residents have focused on people of Chinese descent, and much of the literature is now becoming relatively old. This review examines the current evidence around cultural variations in gambling prevalence, motivations, beliefs, behaviours, and help service utilisation, focusing on gamblers with an East Asian cultural background. Numerous domains in which gambling motivations and behaviours vary across cultural groups are identified, and methodological considerations related to ethnographic gambling research are discussed. This review found that while barriers and predictors to help-seeking for CALD gamblers have been studied extensively, contemporary evidence of help service utilisation and effectiveness in Australia is lacking. Further research providing an accurate assessment of the impacts of gambling for CALD gamblers is needed to ensure that harm minimisation resources are effective for those most vulnerable to harm.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Hypertensive disorders of pregnancy among women of migrant origin in Finland: A population-based study.

INTRODUCTION: Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal mortality and morbidity worldwide. We studied the prevalence of hypertensive disorders of pregnancy among women of migrant origin in Finland. MATERIAL AND METHODS: This study used data from the nationwide Medical Birth Register. Information on the most recent singleton birth of women who delivered between 2004 and 2014 (n = 382 233) was included. Women were classified into nine regional categories based on the country of origin. Women of Finnish origin were the reference group. Generalized linear models adjusted for maternal age, socioeconomic position, smoking in pregnancy, parity, pre-pregnancy body mass index, preexisting diabetes and delivery year were used to study the association between region/country of origin and hypertensive disorders of pregnancy. RESULTS: Among the study population, almost 8% were of migrant origin. The prevalence of hypertensive disorders of pregnancy varied from 1.3% (women of East Asian origin) to 4.2% (women of Sub-Saharan African origin), compared with 4.6% in the Finnish origin reference group. Compared with women of Finnish origin, the risk for any hypertensive disorders of pregnancy after adjustment for confounders was lower for women of migrant origin, with an exception for women of Sub-Saharan African origin. When analyzing gestational hypertension and preeclampsia outcomes separately, Sub-Saharan African origin women had a lower risk for gestational hypertension (risk ratio [RR] 0.41, 95% confidence interval [CI] 0.30-0.56) but a higher risk for preeclampsia (RR 1.77, 95% CI 1.44-2.17) than women of Finnish origin. CONCLUSIONS: In general, women of migrant origin in Finland had a lower risk for any hypertensive disorders of pregnancy and gestational hypertension. The risk for preeclampsia was higher among women of Sub-Saharan African origin and may warrant special attention.

Do East Asians With Normal Glucose Tolerance Have Worse ß-Cell Function? A Meta-Analysis of Epidemiological Studies.

Background: The difference in the relationship between ß-cell function and insulin resistance among Africans, Caucasians and East Asians with normal glucose tolerance (NGT) was not well investigated. Methods: We searched PubMed and Web of Science with keywords and identified studies that used the homeostasis model assessment (HOMA) model to evaluate ß-cell function (HOMA-B) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in certain ethnic groups. We used random-effect model to pool data of HOMAs and compared the combined data among the three ethnic groups using subgroup analysis. Linear regression analysis was used to estimate the coefficient of HOMA-S on HOMA-B in these ethnic groups. Results: We evaluated pooled data of HOMAs in eight African, 26 Caucasian, and 84 East Asian cohorts with NGT, and also 2,392, 6,645 and 67,317 individuals, respectively. The three ethnic groups had distinct HOMA-B but similar HOMA-IR. The regression coefficient of lnHOMA-B on lnHOMA-S was different between Africans and Caucasians (-1.126 vs -0.401, P = 0.0006) or East Asian (-1.126 vs -0.586, P = 0.0087), but similar between Caucasians and East Asians (-0.401 vs -0.586, P = 0.1282). The coefficient in all ethnic groups was similar when age, BMI, and gender were adjusted (African vs Caucasian P = 0.0885, African vs East Asian P = 0.1092, and Caucasian vs East Asian P = 0.6298). Conclusions: In subjects with NGT, East Asians had lower HOMA-B but similar ß-cell response relative to insulin resistance with Caucasians and Africans when age, BMI, and gender were controlled. This result may challenge the allegation that there was an Asian-specific diabetes phenotype with worse ß-cell function.

The East Asian gut microbiome is distinct from colocalized White subjects and connected to metabolic health.

East Asians (EAs) experience worse metabolic health outcomes compared to other ethnic groups at lower body mass indices; however, the potential role of the gut microbiota in contributing to these health disparities remains unknown. We conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area, revealing marked differences between ethnic groups in bacterial richness and community structure. White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian subjects had increased levels of multiple bacterial phyla, fermentative pathways detected by metagenomics, and the short-chain fatty acid end-products acetate, propionate, and isobutyrate. Differences in the gut microbiota between the East Asian and White subjects could not be explained by dietary intake, were more pronounced in lean individuals, and were associated with current geographical location. Microbiome transplantations into germ-free mice demonstrated stable diet- and host genotype-independent differences between the gut microbiotas of East Asian and White individuals that differentially impact host body composition. Taken together, our findings add to the growing body of literature describing microbiome variations between ethnicities and provide a starting point for defining the mechanisms through which the microbiome may shape disparate health outcomes in East Asians.

The community of microbes living in the human gut varies based on where a person lives, in part because of differences in diets but also due to factors still incompletely understood. In turn, this 'microbiome' may have wide-ranging effects on health and diseases such as obesity and diabetes. Many scientists want to understand how differences in the microbiome emerge between people, and whether this may explain why certain diseases are more common in specific populations. Self-identified race or ethnicity can be a useful tool in that effort, as it can serve as a proxy for cultural habits (such as diets) or genetic information. In the United States, self-identified East Asian Americans often have worse 'metabolic health' (e.g. levels of sugar or certain fat molecules in the blood) at a lower weight than those identifying as White. Ang, Alba, Upadhyay et al. investigated whether this health disparity was linked to variation in the gut microbiome. Samples were collected from 46 lean and obese individuals living in the San Francisco Bay Area who identified as White or East Asian. The analyses showed that while the gut microbiome of White participants changed in association with obesity, the microbiomes of East Asian participants were distinct from their White counterparts even at normal weight, with features mirroring what was seen in White individuals in the context of obesity. Although these differences were connected to people's current address, they were not attributable to dietary differences. Ang, Alba, Upadhyay et al. then transplanted the microbiome of the participants into genetically identical mice with microbe-free guts. The differences between the gut microbiomes of White and East Asian participants persisted in recipient animals. When fed the same diet, the mice also gained different amounts of weight depending on the ethnic identity of the microbial donor. These results show that self-identified ethnicity may be an important variable to consider in microbiome studies, alongside other factors such as geography. Ultimately, this research may help to design better, more personalized treatments for an array of conditions.

The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. Design, Setting, and Participants: Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. Exposures: Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts. Main Outcomes and Measures: Depression status was defined based on health records and self-report questionnaires. Results: There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (ß = -0.018, SE = 0.003, P = 4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (ß = 0.028, SE = 0.005, P = 6.48x10-9 for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (ß = -0.003, SE = 0.005, P = .53 for rs4656484 and ß = -0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = -0.212, SE = 0.084), contrary to findings for individuals of European descent. Conclusions and Relevance: These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.

Genetic insights into biological mechanisms governing human ovarian ageing.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

Origin of ethnic groups, linguistic families, and civilizations in China viewed from the Y chromosome.

East Asia, geographically extending to the Pamir Plateau in the west, to the Himalayan Mountains in the southwest, to Lake Baikal in the north and to the South China Sea in the south, harbors a variety of people, cultures, and languages. To reconstruct the natural history of East Asians is a mission of multiple disciplines, including genetics, archaeology, linguistics, and ethnology. Geneticists confirm the recent African origin of modern East Asians. Anatomically modern humans arose in Africa and immigrated into East Asia via a southern route approximately 50,000 years ago. Following the end of the Last Glacial Maximum approximately 12,000 years ago, rice and millet were domesticated in the south and north of East Asia, respectively, which allowed human populations to expand and linguistic families and ethnic groups to develop. These Neolithic populations produced a strong relation between the present genetic structures and linguistic families. The expansion of the Hongshan people from northeastern China relocated most of the ethnic populations on a large scale approximately 5300 years ago. Most of the ethnic groups migrated to remote regions, producing genetic structure differences between the edge and center of East Asia. In central China, pronounced population admixture occurred and accelerated over time, which subsequently formed the Han Chinese population and eventually the Chinese civilization. Population migration between the north and the south throughout history has left a smooth gradient in north-south changes in genetic structure. Observation of the process of shaping the genetic structure of East Asians may help in understanding the global natural history of modern humans.

Glucose-lowering action through targeting islet dysfunction in type 2 diabetes: Focus on dipeptidyl peptidase-4 inhibition.

Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium-glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin.

Comparison of insulin glargine 300 U/mL versus glargine 100 U/mL on glycemic control and hypoglycemic events in East Asian patients with type 2 diabetes: A Patient-level meta-analysis of phase 3 studies.

AIMS: To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM). METHODS: A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100. RESULTS: Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups. CONCLUSION: Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.

Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry.

Modern humans appeared in Europe by at least 45,000 years ago1-5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.

The DASH Diet and Cardiometabolic Health and Chronic Kidney Disease: A Narrative Review of the Evidence in East Asian Countries.

The rising incidence of cardiometabolic diseases and chronic kidney disease (CKD) is a leading public health problem in East Asia. Diet is an important modifiable risk factor; thus, adopting a healthy diet such as the Dietary Approaches to Stop Hypertension (DASH) diet may help combat these chronic diseases. The DASH diet was originally developed in a U.S. population, and East Asia is demographically and culturally different from the U.S. Therefore, it is important to examine the evidence regarding the DASH diet and chronic disease in this unique population. This narrative review summarizes the evidence on the DASH diet and cardiometabolic health and CKD in East Asia. Culturally-modified DASH diets have been developed in some East Asian countries. Studies suggest the DASH diet is effective at lowering blood pressure in this population, though the long-term benefits remain unclear. Evidence also suggests the DASH diet may reduce the risk of type 2 diabetes and metabolic syndrome. Further research indicates the DASH diet and its components may reduce CKD risk. However, recommending the DASH diet in those who already have CKD is controversial, as it conflicts with current CKD dietary guidelines, especially in advanced CKD. Notably, current intakes in the general population differ from the DASH dietary pattern, suggesting public health efforts would be needed to encourage adoption of the DASH diet.

Safety of antithrombotic therapy in East Asian patients.

Antithrombotic agents are widely used on the globe for prevention of thrombotic events such as atherothrombotic events and thromboembolic stroke in atrial fibrillation or for prevention and treatment of venous thromboembolism. However, the net clinical benefit of antithrombotic intervention may differ substantially in various sub-population of patients. Here, the authors attempt to address the risk of serious bleeding in East Asian as compared to the other regions of the world. The community-based epidemiological data suggest numerically higher risk of hemorrhage stroke in East Asian as compared to the globe. Importantly, the life-time risk of ischemic stroke in East Asia is higher than that of the globe. Regarding the serious bleeding risk in East Asians with the use of antithrombotic agents, various clinical trials and international registries provided conflicting information. It is hard to draw generalized conclusion, but there are some specific sub-population in East Asian with higher risk of specific serious bleeding events with the use of specific antithrombotic agents such as the risk of intra-cranial bleeding (ICH) with Vitamin K antagonists. Specific characteristics in East Asian such as higher prevalence of lacunar stroke may contribute higher risk of ICH in East Asian, but the detailed mechanism is still to be elucidated. In conclusion, further investigations are necessary to clarify the specific conditions where the risk of serious bleeding events in East Asian patients differ substantially compared to the global. In addition, further understanding of the mechanisms causing the different bleeding response in specific conditions in East Asian is awaited.

Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. METHODS: We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. RESULTS: Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m2, P<0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P=0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P<0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P=0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P<0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P=0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7, whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P<0.0001). CONCLUSIONS: There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine-based care of individuals with hypertrophic cardiomyopathy.

Public health status of Myanmar refugees in South East Asia: A Malaysian case study.

The United Nations High Commissioner for Refugees (UNHCR) reports over 80 million people are displaced worldwide with approximately 26.3 million categorized as refugees and over a million residing temporarily in South East Asia. Despite the lack of national legislative framework in place for refugees and asylum seekers (RAS), Malaysia hosts approximately 178,140 as registered with UNHCR and the majority originate from Myanmar. In this review, we examine refugees from South East Asia, particularly from Myanmar that have contributed to the largest influx of refugees to this region with a focus on their health status. The present study traces barriers to the health care of refugees in the country of asylum and also the challenges faced by these communities in accessing health services.

How Ethnicity, Expression, and Study Design Influence First Impressions of Approachability.

Over two studies, participants (total N = 642) rated a community sample of photographs of Black, East Asian, and White males who were smiling or portraying a neutral expression to see how participant ethnicity, target ethnicity, and target expression influence judgments of approachability (i.e., trustworthiness, friendliness, and threat). We also examined how a commonly used study design, in which each participant is asked to evaluate different groups of people, may motivate participants to adjust their ratings in an effort to avoid appearing biased. Results showed that the White participant group tended to rate smiling targets as friendlier (Studies 1 and 2) and more trustworthy (Study 1) than did the non-White participant group, which could be due to cultural differences based on majority versus minority status among the participants. In addition, the White participant group tended to rate White targets more positively than did the non-White participant group, suggesting an in-group bias. Finally, differences in results between Studies 1 and 2 suggest that study design can influence the degree of bias responding, highlighting the importance of incorporating a diversity of methods to better understand first impression judgments.

Identification of SHANK2 Pathogenic Variants in a Chinese Uygur Population with Schizophrenia.

Genomic studies on schizophrenia (SCZ) have revealed several candidate genes involved in excitatory synapse function and plasticity associated with its etiology. SHANK2 is a postsynaptic scaffolding protein, which anchors a protein complex connecting NMDAR, AMPAR, and mGluR receptors at excitatory neuronal synapses. Mutations in the SHANK2 gene have been reported to be associated with human autism spectrum disorders (ASDs) and SCZ. To identify variants in the SHANK2 gene and determine the association of SHANK2 with SCZ in the Chinese Uygur population, we conducted targeted sequencing of whole exon regions and exon-intron boundaries of SHANK2 in 1574 SCZ patients and 1481 healthy controls. A total of 149 variants were identified, including six common variants and 143 rare variants. For common variants, rs62622853 and rs3924047 showed allelic significance with SCZ before correction, but the association was eliminated after Bonferroni correction. Seven rare nonsynonymous variants, p.Arg739Trp, p.Pro807Leu, p.Ile854Phe, p.Thr1322Ser, p.Leu1434Arg, p.Val1486Ile, and p.Thr1674Met, occurred only in the patients but not in any of the healthy controls. In silico analysis predicted that p.Arg739Trp, p.Leu1434Arg, and p.Val1486Ile variants are likely to be damaging. The present study suggests that individuals with two novel rare nonsynonymous variants (p.Arg739Trp, p.Leu1434Arg) and p.Val1486Ile variants of SHANK2 might increase the susceptibility to developing SCZ disorder.

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. METHODS: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. RESULTS: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10-8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=-0.242) and non-albumin protein (rg=0.238). CONCLUSION: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.