South Asian Individuals Research Articles

Ethnic Disparities in Lipid Metabolism and Clinical Outcomes between Dutch South Asians and Dutch White Caucasians with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) poses a higher risk for complications in South Asian individuals compared to other ethnic groups. To shed light on potential mediating factors, we investigated lipidomic changes in plasma of Dutch South Asians (DSA) and Dutch white Caucasians (DwC) with and without T2DM and explore their associations with clinical features. Using a targeted quantitative lipidomics platform, monitoring over 1000 lipids across 17 classes, along with 1H NMR based lipoprotein analysis, we studied 51 healthy participants (21 DSA, 30 DwC) and 92 T2DM patients (47 DSA, 45 DwC) from the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction in type 2 dIAbetes mellitus (MAGNA VICTORIA) study. This comprehensive mapping of the circulating lipidome allowed us to identify relevant lipid modules through unbiased weighted correlation network analysis, as well as disease and ethnicity related key mediatory lipids. Significant differences in lipidomic profiles, encompassing various lipid classes and species, were observed between T2DM patients and healthy controls in both the DSA and DwC populations. Our analyses revealed that healthy DSA, but not DwC, controls already exhibited a lipid profile prone to develop T2DM. Particularly, in DSA-T2DM patients, specific lipid changes correlated with clinical features, particularly diacylglycerols (DGs), showing significant associations with glycemic control and renal function. Our findings highlight an ethnic distinction in lipid modules influencing clinical outcomes in renal health. We discover distinctive ethnic disparities of the circulating lipidome and identify ethnicity-specific lipid markers. Jointly, our discoveries show great potential as personalized biomarkers for the assessment of glycemic control and renal function in DSA-T2DM individuals.

Comparing Walker's (2008) skull trait sex estimation standard to proteomic sex estimation for a group of South Asian individuals

This research assesses the potential for misidentification of sex in individuals of South Asian ancestry using the Walker (2008) morphological skull sex estimation standard [1]. Chromosomal sex was assessed using proteomic analysis targeting sex chromosome-specific amylogenic peptides. Results showed that the Walker method produced incorrect classification for 36.7 % of individuals. Overwhelmingly, those incorrectly assigned were chromosomally male. Misidentification was due to males within the group having lower trait scores (i.e., more gracile traits) than the standard would predict. There was also a high level of overlap in trait scores between male and females indicating reduced expression of sexual dimorphism. The use of established multivariate statistical techniques improved accuracy of sex estimation in some cases, but larger osteological data sets from South Asian individuals are required to develop population-specific standards. We suggest that peptide analysis may provide a useful tool for the forensic anthropologist when assessing sex in populations without population specific osteological standards.

Obesity from Clinical Evaluation to Management Local Perspective

For over two millennia, physicians have been aware of the morbidity and mortality linked to overweight and obesity. Various definitions of obesity, as outlined by the World Health Organization (WHO) and the Centers for Disease Control & Prevention (CDC), utilize the Body Mass Index (BMI) to characterize these conditions. Screening for high-risk patients is crucial for guiding lifestyle changes, treatment decisions, and risk reduction strategies.1,2 The assessment involves clinical and laboratory studies to categorize the type and severity of obesity, forming the foundation for effective management. Globally, the prevalence of obesity in 2015 exhibited a rising trend in females compared to males. Between 1980 and 2015, the prevalence surged from 11.1% to 38.3% for males aged 25 to 29 in low to middle-income countries.3 Pakistan ranks tenth among 188 countries, with half of its population classified as overweight or obese. Alarming projections from the World Obese Federation estimate that 5.4 million Pakistani school-aged children will grapple with obesity by 2030, emphasizing the dual challenges of overnutrition and poor nutrition.4,5 World Health Organization data indicates that 58.1% of Pakistanis are overweight, with 43.9% classified as obese. Asian cutoffs, though not globally recognized, suggest that 72.3% of Pakistanis are overweight, with obesity affecting 58.1% of the population. Research by Danielle H. Bodicoat et al. suggests an obesity threshold of 25 kg/m2 for South Asian individuals, coupled with a very high Waist Circumference (WC).6 A WC ≥ 31 inches (80cm) in Asian females and ≥ 35 inches (90cm) in Asian males is considered abnormal. The primary rationale for managing obesity is to mitigate morbidity, including conditions like diabetes, hypertension, dyslipidemia, heart disease, stroke, sleep apnea, and cancer, ultimately reducing mortality. The initial step in managing obesity involves screening to determine the degree of overweight using BMI and waist circumference measurements. However, studies reveal that only 6% of individuals receive ongoing care for weight management, such as prescriptions for obesity medication or referrals to dieticians.7,8 BMI classifications, primarily based on cardiovascular disease (CVD) risk, may underestimate risks for conditions like diabetes in the Asian population. Beyond BMI, measuring waist circumference is essential for identifying adults at increased risk for morbidity and mortality, especially in the BMI range of 25 to 35 kg/m2.9 In addition to physical examinations, measurements of fasting glucose (or glycated hemoglobin [A1C]), thyroid-stimulating hormone (TSH), liver enzymes, and fasting lipids should be conducted.10 Investigating the causes of obesity involves ruling out a sedentary lifestyle, increased caloric intake, and secondary factors. Medical history should include inquiries about medications that cause weight gain and smoking cessation. Weight loss interventions are recommended for those with a BMI exceeding 25 kg/m2, aiming to prevent, treat, or reverse complications associated with obesity. In conclusion, managing obesity in the Pakistani population requires a comprehensive approach involving clinical and laboratory assessments by physicians. This includes evaluating height, weight, BMI, waist circumference, blood pressure, serum triglycerides, serum HDL, cholesterol, fasting blood sugar/HbA1C, history of sleep apnea, medication history, physical activity, and etiological factors. Moreover, physicians should possess knowledge of dietary goals and medications promoting weight loss and consider bariatric surgery if non-responsive to other interventions.

Disentangling Dual Threats: Premature Coronary Artery Disease and Early-Onset Type 2 Diabetes Mellitus in South Asians.

South Asian individuals (SAs) face heightened risks of premature coronary artery disease (CAD) and early-onset type 2 diabetes mellitus (T2DM), with grave health, societal, and economic implications due to the region's dense population. Both conditions, influenced by cardiometabolic risk factors such as insulin resistance, hypertension, and central adiposity, manifest earlier and with unique thresholds in SAs. Epidemiological, demographic, nutritional, environmental, sociocultural, and economic transitions in SA have exacerbated the twin epidemic. The coupling of premature CAD and T2DM arises from increased obesity due to limited adipose storage, early-life undernutrition, distinct fat thresholds, reduced muscle mass, and a predisposition for hepatic fat accumulation from certain dietary choices cumulatively precipitating a decline in insulin sensitivity. As T2DM ensues, the β-cell adaptive responses are suboptimal, precipitating a transition from compensatory hyperinsulinemia to β-cell decompensation, underscoring a reduced functional β-cell reserve in SAs. This review delves into the interplay of these mechanisms and highlights a prediabetes endotype tied to elevated vascular risk. Deciphering these mechanistic interconnections promises to refine stratification paradigms, surpassing extant risk-prediction strategies.

South Asian individuals’ experiences on the NHS low-calorie diet programme: a qualitative study in community settings in England

BackgroundExisting literature examines barriers to the provision of ethnically diverse dietary advice, however, is not specific to total diet replacement (TDR). There is a lack of literature from the UK,...

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial

BackgroundThis exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity.MethodsEMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals.ResultsCompared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m2 (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m2 (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (Pinteraction = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction.ConclusionsThere was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial.Trial registrationClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016).

South Asian adults with ASCVD exhibit a reduction in circulating vascular regenerative cell content compared to White European adults: a sub-analysis of the ORIGINS-RCE CardioLink-13 study

Abstract Background Compared to people of other races and ethnicities, South Asian (SA) adults are disproportionately affected by a higher burden of type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We previously found that compared to individuals of White European (WE) descent with T2D, SA individuals with T2D exhibited profoundly less vascular regenerative (VR) cell content. Given that VR cells critically regulate vessel homeostasis, we postulated that the "vascular regenerative cell exhaustion" phenomenon we had observed may also contribute to the prevalence of ASCVD in SA populations. Purpose The ORIGINS-RCE CardioLink-13 study compared the frequencies of VR cells and cell types in individuals of SA and WE ethnicities with either 1) T2D and cardiovascular-risk factors or 2) documented ASCVD. This sub-analysis was conducted to determine if there are differences in the frequency of circulating VR cells and cell types in SA and WE individuals with ASCVD. Methods Among the 120 self-identified SA and WE adult participants (≥40 years of age), 23 SA and 41 WE individuals had ASCVD. Peripheral blood samples were processed for pro-inflammatory vs. pro-vascular progenitor cell enumeration as well as measurement of reactive oxygen species (ROS) production using a unique high aldehyde dehydrogenase (ALDHhi) activity-based flow cytometry assay in combination with side scatter properties (SSC) and lineage specific cell surface markers to identify progenitor cell populations. Results Compared to samples from the WE participants, the SA adults had a lower frequency of ALDHhiSSClowCD133+ (59% vs. 48%, P<0.001) cells and ALDHhiSSClowCD34+CD133+ (56% vs. 45%, P<0.001) progenitor cells with previously established pro-angiogenic properties. We also observed that SA participants had a decreased frequency of ALDHhiSSClowCD34+CD133+CD45- (0.0019% vs. 0.0005%, P<0.05) cells which may represent a rare population of circulating endothelial progenitor cells with vasculogenic functions. SA participants also exhibited a shift in monocyte polarization from a reparative phenotype towards a pro-inflammatory state, as demonstrated by a decrease in ALDHhiSSCmidCD14+CD163+ (86% vs. 78%, P<0.01) monocytes and an increase in ALDHhiSSCmidCD86+CD163- (8.2% vs. 13%, P<0.01) cells. There were no significant differences in the frequency of circulating granulocytes (ALDHhiSSChi cells) suggesting comparable inflammatory granulocyte burden between SA and WE adults, with no meaningful difference in intracellular ROS production in ALDHhi progenitor cell subsets, as previously observed in participants with T2D. Conclusions South Asian adults with ASCVD demonstrate a loss of vascular regenerative cells suggesting a compromised ability to repair damaged vessels which may contribute to their elevated cardiovascular risk.

Abstract 12995: South Asian Representation in Cardiovascular Disease Randomized Controlled Trials

Introduction: South Asian individuals are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared to individuals of European descent. Although US practice guidelines uniquely recognize South Asian ancestry as a risk-enhancing factor for ASCVD, the degree to which South Asian individuals are included in clinical trials is unknown. We sought to evaluate South Asian representation in major cardiovascular disease (CVD) randomized controlled trials (RCTs) reported in major medical journals. Hypothesis: South Asian individuals are under-represented relative to the global South Asian population in CVD RCTs. Methods: We extracted citations of CVD RCTs reported from 2018 to 2022. Studies were identified as RCTs based on reported randomization of participants and the publication of post-randomization data. We determined self-reported representation rates for South Asian individuals across all studies and further stratified representation rates by clinical trial phase, type of intervention under investigation, and country of origin. Post-randomization participant representation rates were estimated for South Asian individuals and compared to other self-reported racial/ethnic groups. Results: 588,329 participants were enrolled across 128 included trials. Conditions studied included CVA (17.97%), HF (12.50%), CAD (11.72%), HTN (7.81%), ASCVD screening/prevention (7.81%), and others. 2,753 of all CVD RCT participants were South Asian individuals, corresponding to a representation rate of 0.47%. No South Asian individuals had available post-randomization data, whereas post-randomization data were reported for 164,035 white individuals, 20,459 Black individuals, and 6,040 Hispanic individuals. Conclusions: Although South Asian individuals comprise nearly a quarter of the global population and have well-documented excess CVD risk, they represent a small minority of CVD trial participants. No RCTs reported South Asian participant-level data, which limits the generalizability of study findings to South Asians.

Call for Cultural and Language-Concordant Diabetes Care, Nutrition Education, and Self-Management for South Asian Individuals Living in the US

Ethnic South Asian Americans have the highest relative risk of type 2 diabetes mellitus in the US. Culturally tailored and language-concordant diabetes care and nutrition interventions can potentially promote South Asian diabetes management and disease progression. From our perspective, the extent of their use and evaluation in the US settings remains limited. This Perspective characterizes and evaluates the necessity and outcomes of culturally and linguistically adapted lifestyle interventions targeted toward type 2 diabetes mellitus indicators among South Asian individuals in the US. Suggestions for how this education could be modified include emphasizing the cultural and linguistic knowledge and self-awareness of diabetes educators and the sociological and historical factors that influence the cultural and linguistic orientation of diabetes care professionals and their clients. Such strategies could ensure better diabetes education and self-management among South Asian individuals.

Abstract 11370: Comparing Coronary Artery Cross-Sectional Area Among Asymptomatic South Asian, White, and Black Participants: The Masala and Cardia Studies

Introduction: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. Hypothesis: We hypothesized that South Asian participants would have smaller left anterior descending artery (LAD) cross sectional area (CSA) than Black and White participants, and that this association would be attenuated after adjusting for body size (BMI and height) and cardiovascular risk factors. Methods: We compared the LAD CSA (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America study with White and Black participants in the Coronary Artery Risk Development in Young Adults study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to explore differences by race/ethnicity in LAD CSA after adjusting for demographic, BMI, height, coronary artery calcium (CAC), and ASCVD risk factors. Results: We included 3,353 participants: 513 South Asian (44% women), 1286 Black (60% women), and 1554 White (54% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian and White participants by sex. However, South Asian participants had smaller LAD CSA compared to Black participants by sex. After full adjustment for ASCVD risk factors, LAD CSA values were: South Asian women (19.9 mm 2 , 95% CI [18.8 - 20.9]) and men (22.3 mm 2 , 95% CI [21.4 - 23.2]; White women (20.0 mm 2 , 95% CI [19.4 - 20.5]) and men (23.6 mm 2 , 95% CI [23.0 - 24.2]); and Black women (21.6 mm 2 , 95% CI [21.0 - 22.2]) and men (26.0 mm 2 , 95% CI [25.3 - 26.7]) ( Figure 1 ). Conclusions: After accounting for differences in body size, South Asian participants had smaller LAD CSA compared to Black participants, but similar to White participants. Future studies should determine whether LAD CSA is associated with future ASCVD events.

Abstract 17960: Lipoprotein(a) Testing Frequency and Predictors in a Multiethnic Health System

Introduction: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Contemporary practice guidelines recommend incorporating Lp(a) testing into routine clinical practice. We examined the prevalence of Lp(a) testing and characteristics that predicted which individuals underwent testing. Methods: This was a retrospective cohort study. Eligible individuals were patients of a large Northern Californian health system with 2 or more primary care visits between the years 2010 to 2021. Incident density matching was used to select controls matched with a case if a visit date was within ±6 months of the index date of initial Lp(a) test. Prevalence of Lp(a) testing was determined by year. Conditional logistic regression was used to assess the relationship between Lp(a) testing and sociodemographic, clinical, and healthcare utilization variables. Results: Of the 1,484,410 individuals in the cohort, 12,506 (0.84%) had their Lp(a) level checked. The median Lp(a) level was 35 mg/dL and 5,598 (37.78%) of those who underwent testing had a Lp(a) level > 50mg/dL. Among those with Lp(a) testing, there was a higher proportion of Asian individuals and a lower proportion of non-Hispanic Black and Hispanic individuals. In adjusted-analyses, those with a history of ASCVD had over twice the odds of undergoing testing (OR = 2.11 (95% CI = 1.98, 2.26)). South Asian individuals were three times more likely to have undergone Lp(a) testing as compared to non-Hispanic White individuals (OR = 3.25, (95% CI = 3.06, 3.46)), while those identified as non-Hispanic Black and Hispanic were significantly less likely to have undergone Lp(a) testing (OR = 0.7, (95% CI = 0.62,0.8) and 0.62 (95% CI = 0.57, 0.67), respectively). Conclusions: This study examined the real-world clinical testing patterns of Lp(a) over a decade within a large, diverse health system. Expanding access to Lp(a) testing may help reduce disparities within ASCVD risk assessment and treatment.

Ethnic disparities in progression rates for sight-threatening diabetic retinopathy in diabetic eye screening: a population-based retrospective cohort study

IntroductionThe English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse...

Polymorphisms within the SARS-CoV-2 Human Receptor Genes Associate with Variable Disease Outcomes across Ethnicities.

The contribution of human genes to the variability of disease outcomes has been shown to be important across infectious diseases. Studies have shown mutations within specific human genes are associated with variable COVID-19 outcomes. We focused on the SARS-CoV-2 receptors/co-receptors to identify the role of specific polymorphisms within ACE2, TMPRSS2, NRP1 and CD147. Polymorphisms within ACE2 (rs2285666), TMPRSS2 (rs12329760), CD147 (rs8259) and NRP1 (rs10080) have been shown to associate with COVID-19 severity. Using cryopreserved samples from COVID-19-positive African, European and South Asian individuals within South Africa, we determined genotype frequencies. The genetic variant rs2285666 was associated with COVID-19 severity with an ethnic bias. African individuals with a CC genotype demonstrate more severe COVID-19 outcomes (OR = 7.5; 95% CI 1.164-80.89; p = 0.024) compared with those with a TT genotype. The expressions of ACE2 and SARS-CoV-2 viral load were measured using droplet digital PCR. Our results demonstrate rs2285666 and rs10080 were significantly associated with increased SARS-CoV-2 viral load and worse outcomes in certain ethnicities. This study demonstrates two important findings. Firstly, SARS-CoV-2 viral load is significantly lower in Africans compared with individuals of European and South Asian descent (p = 0.0002 and p < 0.0001). Secondly, SARS-CoV-2 viral load associates with specific SARS-CoV-2 receptor variants. A limited number of studies have examined the receptor/co-receptor genes within Africa. This study investigated genetic variants within the SARS-CoV-2 receptor/co-receptor genes and their association with COVID-19 severity and SARS-CoV-2 viral load across different ethnicities. We provide a genetic basis for differences in COVID-19 severity across ethnic groups in South Africa, further highlighting the importance of further investigation to determine potential therapeutic targets and to guide vaccination strategies that may prioritize specific genotypes.

Racial and Ethnic Inequities in Development of Type 2 Diabetes After Gestational Diabetes Mellitus.

To estimate racial and ethnic disparities in type 2 diabetes mellitus after gestational diabetes mellitus (GDM) and to investigate baseline pregnancy clinical and social or structural characteristics as mediators. We conducted a retrospective cohort of individuals with GDM using linked 2009-2011 New York City birth and hospital data and 2009-2017 New York City A1c Registry data. We ascertained GDM and pregnancy characteristics from birth and hospital records. We classified type 2 diabetes as two hemoglobin A 1c test results of 6.5% or higher. We grouped pregnancy characteristics into clinical (body mass index [BMI], chronic hypertension, gestational hypertension, preeclampsia, preterm delivery, caesarean, breastfeeding, macrosomia, shoulder dystocia) and social or structural (education, Medicaid insurance, prenatal care, and WIC [Special Supplemental Nutrition Program for Women, Infants, and Children] participation). We used Cox proportional hazards models to estimate associations between race and ethnicity and 8-year type 2 diabetes incidence, and we tested mediation of pregnancy characteristics, additionally adjusting for age and nativity (U.S.-born vs foreign-born). The analytic data set included 22,338 patients with GDM. The 8-year type 2 diabetes incidence was 11.7% overall and 18.5% in Black, 16.8% in South and Southeast Asian, 14.6% in Hispanic, 5.5% in East and Central Asian, and 5.4% in White individuals with adjusted hazard ratios of 4.0 (95% CI 2.4-3.9), 2.9 (95% CI 2.4-3.3), 3.3 (95% CI 2.7-4.2), and 1.0 (95% CI 0.9-1.4) for each group compared with White individuals. Clinical and social or structural pregnancy characteristics explained 9.3% and 23.8% of Black, 31.2% and 24.7% of Hispanic, and 7.6% and 16.3% of South and Southeast Asian compared with White disparities. Associations between education, Medicaid insurance, WIC participation, and BMI and type 2 diabetes incidence were more pronounced among White than Black, Hispanic, and South and Southeast Asian individuals. Population-based racial and ethnic inequities are substantial in type 2 diabetes after GDM. Characteristics at the time of delivery partially explain disparities, creating an opportunity to intervene on life-course cardiometabolic inequities, whereas weak associations of common social or structural measures and BMI in Black, Hispanic and South and Southeast Asian individuals demonstrate the need for greater understanding of how structural racism influences postpartum cardiometabolic risk in these groups.

ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden

BackgroundCurated databases of genetic variants assist clinicians and researchers in interpreting genetic variation. Yet, these databases contain some misclassified variants. It is unclear whether variant misclassification is abating as these databases rapidly grow and implement new guidelines.MethodsUsing archives of ClinVar and HGMD, we investigated how variant misclassification has changed over 6 years, across different ancestry groups. We considered inborn errors of metabolism (IEMs) screened in newborns as a model system because these disorders are often highly penetrant with neonatal phenotypes. We used samples from the 1000 Genomes Project (1KGP) to identify individuals with genotypes that were classified by the databases as pathogenic. Due to the rarity of IEMs, nearly all such classified pathogenic genotypes indicate likely variant misclassification in ClinVar or HGMD.ResultsWhile the false-positive rates of both ClinVar and HGMD have improved over time, HGMD variants currently imply two orders of magnitude more affected individuals in 1KGP than ClinVar variants. We observed that African ancestry individuals have a significantly increased chance of being incorrectly indicated to be affected by a screened IEM when HGMD variants are used. However, this bias affecting genomes of African ancestry was no longer significant once common variants were removed in accordance with recent variant classification guidelines. We discovered that ClinVar variants classified as Pathogenic or Likely Pathogenic are reclassified sixfold more often than DM or DM? variants in HGMD, which has likely resulted in ClinVar’s lower false-positive rate.ConclusionsConsidering misclassified variants that have since been reclassified reveals our increasing understanding of rare genetic variation. We found that variant classification guidelines and allele frequency databases comprising genetically diverse samples are important factors in reclassification. We also discovered that ClinVar variants common in European and South Asian individuals were more likely to be reclassified to a lower confidence category, perhaps due to an increased chance of these variants being classified by multiple submitters. We discuss features for variant classification databases that would support their continued improvement.

Assessing the performance of European-derived cardiometabolic polygenic risk scores in South-Asians and their interplay with family history

Background & aimsWe aimed to assess the performance of European-derived polygenic risk scores (PRSs) for common metabolic diseases such as coronary artery disease (CAD), obesity, and type 2 diabetes (T2D) in the South Asian (SAS) individuals in the UK Biobank. Additionally, we studied the interaction between PRS and family history (FH) in the same population.MethodsTo calculate the PRS, we used a previously published model derived from the EUR population and applied it to the individuals of SAS ancestry from the UKB study. Each PRS was adjusted according to an individual’s genotype location in the principal components (PC) space to derive an ancestry adjusted PRS (aPRS). We calculated the percentiles based on aPRS and stratified individuals into three aPRS categories: low, intermediate, and high. Considering the intermediate-aPRS percentile as a reference, we compared the low and high aPRS categories and generated the odds ratio (OR) estimates. Further, we measured the combined role of aPRS and first-degree family history (FH) in the SAS population.ResultsThe risk of developing severe obesity for SAS individuals was almost twofold higher for individuals with high aPRS than for those with intermediate aPRS, with an OR of 1.95 (95% CI = 1.71–2.23, P < 0.01). At the same time, the risk of severe obesity was lower in the low-aPRS group (OR = 0.60, CI = 0.53–0.67, P < 0.01). Results in the same direction were found in the EUR data, where the low-PRS group had an OR of 0.53 (95% CI = 0.51–0.56, P < 0.01) and the high-PRS group had an OR of 2.06 (95% CI = 2.00-2.12, P < 0.01). We observed similar results for CAD and T2D. Further, we show that SAS individuals with a familial history of CAD and T2D with high-aPRS are associated with a higher risk of these diseases, implying a greater genetic predisposition.ConclusionOur findings suggest that CAD, obesity, and T2D GWAS summary statistics generated predominantly from the EUR population can be potentially used to derive aPRS in SAS individuals for risk stratification. With future GWAS recruiting more SAS participants and tailoring the PRSs towards SAS ancestry, the predictive power of PRS is likely to improve further.

Ethnic Minority Microparticles have Distinct Pro-Thrombotic and Pro-Oxidative Phenotypes and Interact Differentially with Endothelial Cells in vitro: Implications for Risk to Cardiovascular Disease

Ethnic minority individuals are disproportionately susceptible to endothelial dysfunction and cardiovascular disease (CVD). Microparticles (MP) are biologically active membrane-bound nanovesicles released from cells that act as biomolecular shuttles. Plasma MP was isolated from healthy White, Black African, and South Asian individuals and analysed using flow cytometry. Their effects and interactions were assessed using fluorescence, confocal, and scanning electron microscopy. Total MP and a sub-population of smaller MP associated with dysfunction and disease progression were significantly increased in Black African individuals. Pro-thrombotic and pro-oxidant MP were substantially more numerous in Black African individuals. The tissue factor activity of ethnic minority MP was significantly greater than White MP. Ethnic minority MP induced significantly greater functional changes and morphology to an endothelial cell line in vitro and integrated into endothelial cells noticeably more than White MP. These data imply distinct differences in ethnic minority MP, suggesting a role in CVD susceptibility.

1521-P: Healthy, Nonobese South Asian Men Have Both Greater Peripheral and Hepatic Insulin Resistance than Chinese Men

Introduction: South Asian individuals, despite a healthy weight, are at a greater risk of type 2 diabetes mellitus than Chinese individuals. This may be secondary to higher peripheral and/or hepatic insulin resistance (IR). Using the 2-stepped hyperinsulinemic-euglycemic clamp, we examined the differences in peripheral and hepatic insulin resistance between healthy and non-obese South Asian and Chinese men. Bioimpedance analysis was performed to assess body composition. Methods: A 2-stepped hyperinsulinemic-euglycemic clamp was performed together with a “pancreatic” clamp by infusing somatostatin. A low-dose insulin (10 mU/m2/min) was infused for 2 hours, followed by high-dose insulin infusion (40 mU/m2/min) for 2 hours. Intravenous 20% glucose was infused to maintain euglycemia (blood glucose = 95-100 mg/dl) for the clamp duration. A higher M value (mg glucose per kg bodyweight per minute) during low-dose insulin infusion reflects lower hepatic IR while a higher M value during high-dose insulin infusion reflects lower peripheral IR. Results: The 2 groups (26 South Asian and 26 Chinese men) had similar age (27.3 vs 26.2 years, p = 0.338), but the South Asian group had slightly higher BMI (24.6 vs 22.9 kg/m2, p = 0.027) and body fat % (23.9 vs. 20.6%, p &amp;lt; 0.05). During low-dose step, the M-value was lower among South Asians compared to Chinese (0.8 ± 0.58 vs. 1.1 ± 0.55 mg/kg/min, p = 0.027). During high-dose step, the M-value was also lower among South Asians compared to Chinese (3.2 ± 2.6 vs. 5.2 ± 3.3 mg/kg/min, p = 0.015). The differences in the M-values between South Asian and Chinese individuals remained significant after correcting for body weight and fat-free mass. Conclusion: Despite a healthy weight, young South Asians have both greater hepatic and peripheral muscle IR than Chinese. Disclosure A.Y.L.Lim: None. H.Tan: None. C.Khoo: None. Funding National Medical Research Council of Singapore (MOH-CNIG19NOV-0002)

1477-P: Improved Diabetes Risk Prediction Using Ancestry-Specific Polygenic Score—Results from the Asian Indian Diabetic Heart Study/Sikh Diabetes Study

Background: Genome-wide polygenic risk scores (PRS) have shown high specificity and sensitivity in predicting type 2 diabetes (T2D) risk in Europeans. However, PRS-driven information on other ethnic groups is sparse, including Asian Indians (AI), who have a heightened risk for T2D. We examined the predictive efficacy of ancestry-derived (PRSAI) and European-derived (PRSEU) with a clinical risk score (CRS) of T2D. Methods: Weighted PRSs were computed using 2921 variants (common and rare) from (Punjabi/Sikh) genome-wide association studies and 432 variants from European meta-analyses studies in 4,602 individuals (2,574 cases and 2,028 controls) of the Asian Indian Diabetes Heart Study/Sikh Diabetes Study. Both Ancestry-specific PRSAI and European PRSEU were validated on 9372 UK Biobank South Asian individuals (1943 cases/7429 controls). Results: Ancestry-specific PRSAI showed 36.2% improved efficacy than PRSEU in Punjabi Asian Indians. Similarly, Ancestry-specific PRSAI was 18.6% superior to PRSEU in Asian Indians from UKBB based on Nagelkerke’s R2. Sensitivity analysis explained enhanced sensitivity (area under the curve-AUC) of ancestry-specific PRS over PRSEU in predicting T2D risk. Conclusions: Our data suggest expanding genetic studies in diverse ethnic groups to exploit the full potential of PRS to improve health outcomes. More genetic evaluations, specifically in understudied/underrepresented populations, would help increase the transferability of genome-wide polygenic scores across racial and ethnic groups to make their integration into clinical practice easier. Disclosure G.K.Tung: None. M.Rout: None. D.K.Sanghera: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082766, R01DK118427); Presbyterian Health Foundation

A qualitative study on lived experience of self-harm in South Asians in the UK: From reasons to recovery.

Self-harm rates and clinical presentations differ by ethnicity. South Asian women are at risk of self-harm. Previous research suggested investigating individuals' experiences with self-harm with qualitative studies in developing self-harm prevention strategies. This research aims to explore self-harm experiences among South Asians in the United Kingdom. Qualitative study. Participants were recruited via third-sector organizations and online platforms. Semi-structured interviews were conducted with 11 South Asian individuals with a history of self-harm living in the United Kingdom. The data were analysed based on a reflective thematic analysis approach. Results revealed four main themes: (1) reasons for self-harm; (2) recovery journey; (3) culture and mental health; and (4) the transition to suicidal thoughts and behaviours. Reasons for self-harm included negative life circumstances, social life difficulties, challenges faced during COVID-19 and mental health problems. Participants described their recovery journey by acknowledging the role of professional help, self-care, psychoeducation and personal growth, improving social relationships,and faith and spirituality. Cultural factors included generational differences and stigma. Culturally adapted psychological interventions were perceived as promising. The reported transition from self-harm to suicidal behaviours was linked to experiencing major stressful life events and the use of severe methods of self-harm. The findings suggest that socio-cultural factors impact mental health and recovery processes among South Asians. Mental health services should consider improving culturally sensitive clinical practices in responding to self-harm among South Asian communities.