Caucasian Ethnicities Research Articles

Meta-analysis investigating the impact of the LEPR rs1137101 (A>G) polymorphism on obesity risk in Asian and Caucasian ethnicities

Obesity is a chronic condition which is identified by the buildup of excess body fat caused by a combination of various factors, including genetic predisposition and lifestyle choices. rs1137101 (A > G) polymorphism in the CHR1 domain of LEPR protein linked to different diseases including obesity. Nevertheless, the connection between this polymorphism and the likelihood of developing obesity has not been determined definitively. Therefore, a meta-analysis was conducted to assess the relationship between rs1137101 and the risk of obesity. The meta-analysis included all studies meeting pre-defined criteria, found through searching databases up until February 2023. A combined odds ratio with a 95% confidence interval was estimated as overall and in continent subgroups for homozygous, heterozygous, recessive, dominant and allelic models using the fixed or the random-effects model. The meta-analysis identified 39 eligible studies with cases and controls (6099 cases/6711 controls) in 38 articles under different ethnic backgrounds. The results indicated a significant relationship between rs1137101 and the likelihood of developing obesity in each of the genetic models [the homozygous model (GG vs. AA: 95% Confidence Interval = 1.12–1.73, Odds Ratio = 1.39, P value = 0.003); the heterozygous model (AG vs. AA: 95% Confidence Interval = 1.07–1.42, Odds Ratio = 1.23, P value = 0.005); the dominant model (AG/GG vs AA: 95% Confidence Interval = 1.10–1.49, Odds Ratio = 1.28, P value = 0.001); the recessive model (GG vs AA/AG: 95% Confidence Interval = 1.02–1.45, Odds Ratio = 1.21, P value = 0.03); and the allelic model (G vs A; 95% Confidence Interval = 1.07–1.33, Odds Ratio = 1.19, P value = 0.002)] tested. Additionally, with an FDR <0.05, all genotypic models demonstrated statistical significance. The association remained significant among subgroups of Asian and Caucasian populations, although analysis in some genetic models did not show a significant association. Begg's and Egger's tests did not show publication biases. In sensitivity analysis, one particular study was found to have an impact on the Recessive model's significance, but other models remained unaffected. The current meta-analysis found significant indications supporting the association between rs1137101 and obesity. To avail a deeper understanding of this association, future research should include large-scale studies conducted in diverse ethnic populations.

Plain radiographic indices are reliable indicators for quantitative bone mineral density in male and female patients before total hip arthroplasty

Osteoporosis is underdiagnosed in patients undergoing total hip arthroplasty (THA). Bone mineral density measurement by dual-energy X-ray absorptiometry (DXA) is the gold standard, but indices on plain hip radiographs also seemed to be reliable screening tools in female or Asian ethnicities in previous studies. Given the lack of knowledge about male patients and Caucasian ethnicities, this study was conducted to evaluate plane hip radiographic indices as a screening tool for osteopenia and osteoporosis in Caucasian female and also male patients before undergoing THA. A retrospective analysis of 216 elderly patients with pre-existing DXA before hip arthroplasty was performed and four indices were calculated on plain hip radiographs: Canal-Flare-Index (CFI), Canal-Calcar-Ratio (CCR), Canal-Bone-Ratio (CBR) 7 and 10 cm below the lesser trochanter. They were correlated with femoral neck DXA T-scores by Pearson’s correlation and intraclass correlation coefficient, and a ROC analysis was performed. A total of 216 patients (49.5% male) were included. CBR-7 and -10 were highly correlated (p < 0.001) with femoral neck T-score in males (Pearson’s correlation CBR-7 r = − 0.60, CBR-10 r = − 0.55) and females (r = − 0.74, r = − 0.77). CBR-7 and -10 also showed good diagnostic accuracy for osteoporosis in the ROC analysis in males (CBR-7: AUC = 0.75, threshold = 0.51; CBR-10: 0.63; 0.50) and females (CBR-7: AUC = 0.87, threshold = 0.55; CBR-10: 0.90; 0.54). Indices such as the Canal Bone Ratio (CBR) 7 or 10 cm below the lesser trochanter on plain hip radiographs are a good screening tool for osteopenia and osteoporosis on plain hip radiographs and can be used to initiate further diagnostics like the gold standard DXA. They differ between male and female patients.

Abstract 14601: Increased Risk of Major Adverse Cardiovascular Events Attributed to Lipoprotein(a) Across Current Atherosclerotic Cardiovascular Disease Risk Categories

Introduction: AHA guidelines recommend measurement of lipoprotein(a) [Lp(a); an inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD)] in individuals with a family or personal history of premature ASCVD. Lp(a) measurement is also recommended for recalibrating the 10-year risk score for borderline or intermediate risk individuals. However, there is limited evidence on the risk of MACE attributed to elevated Lp(a) across ASCVD risk categories. Hypothesis: To assess the impact of elevated Lp(a) levels on MACE across ASCVD 10-year risk categories. Methods: This observational, retrospective study included a primary prevention cohort of Caucasian and Black ethnicities from the UK Biobank (2006-2020). Associations of Lp(a) level (categories of 105-150, 150-190, 190-215, and 215-260 nmol/L were compared to Lp(a) &lt;105 nmol/L) with time to first MACE and MI were assessed using Cox proportional hazard models adjusted for age, sex, and ethnicity, stratified by ASCVD 10-year risk score category. Results: The cohort (N=362,061) included 55.2% female, 94.3% Caucasian and 1.6% Black. MACE incidence rates (IR, per 100 person/years) increased with 10-year ASCVD risk score: low risk IR=0.14 (n=161,183), intermediate risk IR=0.72 (n=121,272) and high-risk IR=1.52 (n=27,733). Within and across these risk categories, elevated Lp(a) conferred a significant increase in risk of MACE and myocardial infarction (MI). In the low-risk category, HRs ranged from 1.15-1.55 (MACE) and 1.32-1.72 (MI), in the intermediate risk category HRs ranged from 1.19-1.51 (MACE) and 1.37-1.77 (MI), and in the high-risk category HRs ranged from 1.12-1.55 (MACE) and 1.14-1.76 (MI) (Figure 1). Conclusions: Our study demonstrates that elevated Lp(a) increases the risk of MACE independently of ASCVD risk score. Measuring and considering elevated Lp(a) levels as part of individual ASCVD risk assessment in routine clinical practice may help improve the risk predication.

The impact of ethnicity on abnormal electrocardiographic findings in elite Brazilian football players: B-pro foot ECG pilot study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Black athletes may be more likely to have uncommon electrocardiogram findings than white athletes. The prevalence of abnormal electrocardiographic findings in elite Brazilian football players (EBFP) of different ethnicities is unknown. Purpose To compare the prevalence of these changes and their correlation with the echocardiogram and cardiac magnetic resonance (CMR) in Caucasian, Mixed-race (MR), and Afro-Brazilian (AB) EBFP. Methods A multicenter cross-sectional descriptive study was conducted with exams performed on EBFP as a pre-participation assessment from February 18, 2002, through October 20, 2022. Results 4,363 EBFP from 51 professional clubs (from all five regions of Brazil; 15 states, and 21 cities), aged 15-35 years (median: 19 years; IQR: 16-23) were evaluated. 2,027 were Caucasians, 1,324 were MRs, and 1,012 were ABs. T-wave inversion (TWI) in leads II and aVF (4.2% vs. 2.3%), V5 (4.0% vs. 1.7%), and in V5-V6 (3.0% vs. 1.4%) was more common in AB than in Caucasian players, respectively (P = 0.002 for all comparisons). In addition, AB demonstrated a significantly greater prevalence of inferolateral TWI (2.3%) than Caucasian (1.1%), and MR (1.3%) EBFP, respectively. TWI in leads V1-V3 in Caucasians or MRs &amp;gt;16 years was present in 0.9% (30/3,351). PR interval ≥400 ms was observed in one Caucasian and in one AB athlete. The Wolff-Parkinson-White pattern was identified in two Caucasians, and a suggestive case of a type 2 Brugada Pattern in one Caucasian. Overall, 208 (4.8%) EBFP had electrocardiographic changes considered to be abnormal (4.5% in Caucasians, 4.8% in MRs, and 5.2% in ABs). Of these, 150/208 (72.1%) underwent an echocardiogram. Isolated inferior TWI was not associated with echocardiographic abnormalities (n = 25), similar to persistent juvenile TWI patterns (in Caucasians or MRs). However, TWI in inferolateral leads was associated with 10.5% echocardiographic abnormalities (4/38). Of these, 75% (3/4) had abnormal CMR findings: one AB with hypertrophic cardiomyopathy (CMP), and two Caucasians with non-compaction CMP; one Caucasian with an abnormal echocardiogram demonstrated normal CMR, suggesting "athlete's heart". Finally, one AB had normal echocardiogram results, but the CRM showed a finding compatible with apical hypertrophic CMP. Conclusion In this large cohort of EBFP, approximately 5% of the electrocardiographic findings were considered abnormal. In those with inferolateral TWI, the use of CMR may indicate the presence of potentially malignant cardiac disease, even with normal echocardiographic findings. AB ethnicity was associated with a higher prevalence of TWI in the inferior and/or lateral leads in comparison to Caucasian or MR ethnicities.

Comparison of postprandial glycaemic response following wholemeal bread meal consumption between healthy young adults with Asian and Caucasian ethnicities

Comparison of postprandial glycaemic response following wholemeal bread meal consumption between healthy young adults with Asian and Caucasian ethnicities

Development of Merkel Cell Carcinoma in a Patient Receiving Rituximab

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and aggressive dermatological neoplasm. It is commonly reported in Caucasian ethnicities, and almost 50% of the patients have a concomitant malignancy and are on immunosuppressive chemotherapy. Here, we present a 79-year-old woman with a history of relapsed Stage II, grade III follicular lymphoma, receiving maintenance rituximab infusions. She presented with a raised erythematous papule on her left cheek. An excisional biopsy of the lesion confirmed a diagnosis of Merkel cell carcinoma. After which, she underwent a wider excision with 1-2 cm margins. PET scan did not reveal any FDG-avid uptake lesions that would be concerning for metastatic disease. However, she underwent a sentinel lymph node biopsy which was also negative. Thus, the diagnosis was finalized as Stage I (T1 N0 M0) MCC. There are only two reported cases in literature about the significant progression of Merkel cell carcinoma in patients who coincidentally were receiving rituximab as a part of treatment for another disease. This raises questions for future investigation and research on whether there is a direct association between rituximab use specifically and the rapid growth of MCC.

Breast cancer risk predictions by birth cohort and ethnicity in a population-based screening mammography program.

To examine whether birth cohorts affect the risk of breast cancer for East Asian, First Nations, African, South Asian and Caucasian ethnicities in British Columbia (BC). We used Cox PH models adjusted for well-known risk factors, such as age, breast density, mammographic features on false positives, and family history, to examine risk of breast cancer among East Asian, First Nations, African and South Asian ethnicities, relative to Caucasian, across three birth cohorts. There were 813,280 participants and 11,166 in situ and invasive breast cancer diagnoses. East Asians screened in BC were found to have a lower risk of breast cancer in the birth cohort born pre-1946 compared to Caucasian, but there was no statistically significant decrease for East Asians born after 1946. First Nations had an increased risk of breast cancer compared with Caucasian for all birth cohorts ranging from 1.1 to 2.0x the risk, which was statistically significant for those born after 1965. South Asians showed a statistically significant decrease in risk ranging from 0.58 to 0.81x lower compared with Caucasians for all birth cohorts. Risk of breast cancer for South Asians living in BC was found to be lower than Caucasians for each birth cohort examined, while East Asians had a comparable risk of breast cancer, First Nations had a consistently higher risk than Caucasians. When accounting for birth cohort, compared to Caucasians, South Asians have a decreased risk, First Nations have an increased risk, and East Asians have a similar risk of breast cancer.

Reference ranges for functional and structural echocardiographic parameters in asian athletes: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Physiologic cardiac remodelling is common in elite athletes, including changes such as increased left ventricle size and left ventricular wall thickness. These changes often overlap with those from pathological cardiac conditions - for instance dilated cardiomyopathy and hypertrophic cardiomyopathy - leading to diagnostic uncertainty. The availability of reference ranges specific to elite athletes, particularly Caucasian and Black ethnicities, facilitates accurate differentiation between physiology and pathology. However, there remains a paucity of Asian data despite an increased representation in global sport. Purpose To perform a systematic review and meta-analysis of cardiac imaging studies in Asian elite athletes and obtain reference values for commonly utilised parameters in this population. Methods We searched MEDLINE via PubMed, Embase, and the Cochrane Database for relevant studies from inception till 27th July 2021. We included observational studies that reported relevant cardiac imaging parameters in Asian elite athletes. We excluded studies that did not report gender-specific cardiac imaging parameters. After study selection and data extraction, we performed random effects meta-analysis of means to obtain the weighted mean of each relevant cardiac imaging parameter stratified by gender. Results We included a total of eight studies with relevant echocardiographic data from East Asia, South Asia and West Asia which comprised a total of 799 male and 206 female elite athletes participating in endurance and mixed sport disciplines. We excluded data pertaining to athletes participating in skill and power disciplines in a post-hoc manner due to paucity of data and extreme data ranges. The weighted mean left ventricular mass (g) was 211.5 (95% CI 202.6 - 220.3, I2 = 85.8%) for males, and 139.3 (95% CI 132 - 146.7, I2 = 88.2%) for females. The weighted mean left ventricular mass indexed to body surface area (g/m2) was 103.1 (95% CI 99.2 - 106.9, I2 = 79.4%) for males, and 75.1 (95% CI 71.5 - 78.6, I2 = 86.1%) for females. For left ventricular end diastolic diameter (mm), the weighted mean was 54.4 (95% CI 53.1 - 55.7, I2 = 97.3%) for males, and 47.2 (95% CI 46.2 - 48.3, I2 = 89.3%) for females. Lastly, the weighted mean left ventricular wall thickness (mm) was 9.9 (95% CI 9.6 - 10.2, I2 = 91.3%) for males, and 8.7 (95% CI 8.5 - 9, I2 = 80.7%) for females. Conclusions This is the first meta-analysis that provides preliminary echocardiographic reference ranges for Asian elite athletes. Statistical heterogeneity, however, is high in most outcome measures. This is likely due to the presence of confounders such as study demographics. Due to a paucity of studies, further subgroup or stratified analyses could not be performed meaningfully. More large-scale observational studies are required such that more sport, gender or region-specific data could be generated.

MO203: Minimal Change Disease Secondary to SARS-COV-2 (COVID-19) Infection: A Report of 2 Cases and Review of Related Literature

Abstract &amp;gt;BACKGROUND AND AIMS The COVID-19 pandemic has brought to the forefront a wide spectrum of renal injuries that included glomerulopathies, some of which were recently highlighted in various case reports. These consist of focal and segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).1 These changes were found among seemingly vulnerable populations such as the African American and Caucasian ethnicities with paucity of reports among other races. We present two cases of biopsy-confirmed MCD secondary to COVID-19 infection among adult Filipino patients. METHODS Case Report RESULTS: Case 1 A 40-year-old Filipino female with a history of right total mastectomy 2 years prior for a low-grade phyllodes tumor and no other medical comorbidities was admitted due to stillbirth. She was noted to have bipedal edema with a positive COVID-19 RT-PCR swab. Further workup revealed a serum creatinine 1.04 mg/dL, urine RBC 1/HPF and a 24-h urine protein of 9.22 g with hypoalbuminemia and dyslipidemia. Serologic workup was noted to be negative. She was started on Losartan, Atorvastatin, and Furosemide. A kidney biopsy was performed which demonstrated unremarkable light microscopy and immunofluorescence and widespread podocyte-foot process effacement. These biopsy findings were interpreted to be consistent with minimal change disease. She was started on Prednisone at 1 mg/kg/day with continuation of both Losartan and Atorvastatin. Six weeks after, the patient achieved complete remission with resolution of both hypoalbuminemia and dyslipidemia. She also reports no further recurrence of edema. Case 2 A 61-year-old Filipino male with a history of type 2 diabetes mellitus, hypertension, dyslipidemia and mild COVID-19 infection 4 months prior now presented with diarrhea. A routine COVID-19 RT-PCR swab revealed a re-infection. Physical examination noted bipedal edema. Further workup demonstrated a serum creatinine 3.39 mg/dL, urine RBC 2/HPF and urine ACR 2.6 g/g. Serologic tests were negative. He was diagnosed with Nephrotic Syndrome and underwent kidney biopsy. Findings showed an unremarkable light microscopy and immunofluorescence with widespread podocyte-foot process effacement. These findings were found to be consistent with minimal change disease and acute tubular injury. He was started on Prednisone (1 mg/kg/day), Losartan, Furosemide and Atorvastatin. Eight weeks later, the patient achieved complete remission with resolution of edema. CONCLUSION It is currently suspected that APOL1 risk variants found in reported cases of COVID-19-associated glomerulopathies are underlying toxic gain-of-function mutations that drive kidney disease.2 It is interesting to note that APOL1 renal risk variants are found exclusively in African-derived chromosomes and are rarely found among European or Asian chromosomes.3 Even though an APOL1 genotyping was not performed, our case reports provide the first examples of MCD among individuals without a high-risk genotype (APOL1) by epidemiology and enlarge the literature on MCD in COVID-19. We posit that there may be other underlying predispositions or mechanisms that may be driving glomerulopathy formation among COVID-19 patients aside from their inherent APOL 1 risk. Both of our patients were started on steroid therapy with a tapering regimen and achieved complete remission on subsequent follow-up. Existing reports suggest that most cases of COVID-19-associated MCD will often achieve resolution of AKI and proteinuria with steroid therapy, even in those with high-risk APOL1 genotype, emphasizing the need for an accurate histologic classification.4

No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis.

The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)-CLOCK SNP rs1801260 and ADH4 SNPs rs1800759, and rs1126671-with CH were studied previously, but the results were inconsistent. Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software. Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on CLOCK rs1801260, five on ADH4 rs1800759, and three on ADH4 rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the CLOCK gene, rs1800759 and rs1126671 in the ADH4 gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95-1.28; p=0.19; rs1800759: OR 1.06, 95% CI: 0.93-1.22; p=0.37; and rs1126671: OR 1.09, 95% CI: 0.92-1.28; p=0.32). We found no significant associations between the three SNPs (rs1801260 in the CLOCK gene and rs1800759 and rs1126671 in the ADH4 gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta-analysis.

САМОСПРИЙНЯТТЯ ЗМІН СПОСОБУ ЖИТТЯ ТА БЛАГОПОЛУЧЧЯ, ЗУМОВЛЕНИХ СОЦІАЛЬНИМ ДИСТАНЦІЮВАННЯМ ПІД ЧАС COVID-19 СЕРЕД СТУДЕНТІВ-МЕДИКІВ (дослідження у Львові, Україна)

Social distancing related to the coronavirus disease (COVID-19) pandemic caused by SARS COV2 is an important precautionary measure, implemented by WHO approximately 1 year ago. At the same time, it is a large-scale stressor that has led to multiple changes in the lifestyle around the world. In this crisis, the well-being and health of medical students who belong to the individuals with a high risk of distress in the population are very important for society. The purpose of this research is to study the impact of COVID-19-related stay-at-home policy, social isolation, online academic learning, and working on the medical students' lifestyle and well-being focusing on their self-perception of telecommunication technologies, social media, as well as on the psychophysiological state, and eating behavior of medical students of Danylo Halytsky Lviv National Medical University (LNMU). Methods. A prospective, cohort study was carried out on 273 medical students of the LNMU via an anonymous online survey using Google Forms. 273 people of different ethnicities answered the original questionnaire, which includes: 1) general questions (age, gender, ethnicity, family, education, work, and economic status); 2) issues related to the use of social media; 3) questions about the impact of social distancing on lifestyle; 4) the scale of stress perception. Results: The cohort for the study consisted of 166 women and 107 men in the following age groups: from 17 to 24 — 92 %, 25–31 — 4 %, 35–44 — 2 %, and over 45 years — 2 %. Ethnic groups included Asian — 47 %, Caucasian — 41 %, African — 7 %, Hispanic — 3 %, and multiracial people — 2 %. Social exclusion during COVID-19 was found to be caused by a change in the use of social media, more time spent on using them by all respondents. Among these, 88 % acknowledge that social media have a great impact and 71 % of responders learn basic information about the pandemic via social media. However, 52 % doubt the reliability of the information. The feeling of anxiety, panic, which characterized the perception of stress caused by information on social media, was reported by 56 % of respondents. Almost all respondents changed their lifestyle, which was characterized by physical inactivity and changed eating behavior. About 60 % of respondents reported overeating in the evening and at night (19:00 — 5:00) and almost half of all respondents reported weight gain in the last year. All respondents know about the benefits of physical activity to overcome signs of psycho-emotional stress, but only about 10 % of respondents exercise regularly. There were no differences in the responses from students belonging to the Caucasian group or other ethnicities. Conclusions. The lifestyle of student youth, their eating behavior, and psycho-emotional state are being modified during COVID-19. Social media is an important informative factor in the context of social exclusion and the fight against chronic stress

Application of noninvasive magnetomyography in labour imminency prediction for term and preterm pregnancies and ethnicity specific labour prediction

This paper investigates the application of magnetomyography (MMG) signals from uterine contractions in pregnant patients towards the prediction of labour imminency within or above 48 h. The study utilised the MMG signals collected from a host of pregnant patients retrieved from a Physionet database, which also contained information regarding patients’ ethnicity and pregnancy. Utilising​ the information available in addition to the dataset, the study investigated the prospect of designing an ethnic specific labour imminency classifier to allow for an enhanced prediction, with an emphasis on Black and Caucasian ethnicities due to the nature of the data. Using an extended feature vector and a support vector machine (SVM) classifier, it was seen that the labour imminency was enhanced across the various classifier metrics considered in the ethnic specific classifier when compared with the generalised classifier. The results from the classification exercise, which considered the fusion of MMG signal information with the information on patients’ records, showed greater variability and a slightly lower classifier performance, thus suggesting that the MMG signals present a more reliable way of classifier training. Subsequent work in this area would now involve the application of optimisation algorithms to select an optimal number of electrodes that can be used for data acquisition, and thereby contributing towards the lowering of the cost associated with the implementation of the method using the MMG instrumentation.

New germline mutations in BRCA1, ATM, MUTYH, and RAD51D genes in Tuvans early-onset breast cancer patients.

In Russia, more than 50,000women are diagnosed with breast cancer (BC) every year. Russia is a multinational country- about 200ethnic groups live on its territory. Khakass, Buryats, Tuvans and other ethnic groups show higher rate of increase in BC incidence and a younger age of first diagnosed BC compared to Caucasian ethnicities. We focused on Tuvan ethnic group to find specific genetic aberrations associated with BC. There are no BC prevention models as well as standards for the treatment of inherited BC in Tuvans. In this context, the search for genetic markers of early cancer detection and the development of criteria for therapy response are relevant. To identify hereditary mutations in BC-associated genes in Tuvan women. 24patients with early-onset BC (range, 25to 46years) were enrolled in the study. Genomic DNA isolated from blood samples was used to prepare libraries using a capture-based target enrichment kit covering 27genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53and XRCC2). Next-generation sequencing was performed using the Illumina NextSeq500System. In our study, one pathogenic mutation was detected in BRCA1 (rs80357868) gene (prevalence of 4%, 1/24). We identified the truncating 3875_3878delGTCT mutation of BRCA1gene in Tuvans BC patient aged 34years. We also detected three mutations that were probably damaging by PolyPhen2and/or deleterious by SIFT in ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes. To the best of our knowledge, this is the first report that describes the highly pathogenic variant in the BRCA1gene (rs80357868) and possibly damaging (PolyPhen2) germline variants in the ATM (rs781023264), MUTYH (rs199840380) and RAD51D (rs145309168) genes in young Tuvans BC patient.

The Relationships Between Reproductive History, Ethnicity and Alzheimer’s Disease Incidence

Introduction: In recent years, it has been shown that postmenopausal women have a greater risk of developing Alzheimer’s Disease (AD) than their male counterparts. Additionally, greater parity in postmenopausal women is associated with increased AD prevalence. Menopause and childbirth, two factors that affect estrogen levels, are believed to contribute to this health disparity, as estrogen plays an important role in neuroprotection. In addition, few studies have considered the effect of ethnicity on AD incidence in postmenopausal women. It is important to consider the role of ethnicity in the development of effective AD prevention methods for diverse ethnicities. This study seeks to a) investigate the link between increased parity and the development of AD in postmenopausal women of different ethnicities, and b) investigate the effectiveness of estrogen replacement therapy (ERT) in reducing the risk of AD. Methods: This protocol comprises two studies. Study 1 will include neurological assessment of 200 postmenopausal women to determine AD incidence. These women will be from African, Caucasian, Asian, and Latin ethnicities. The second study will be a randomized, placebo-controlled clinical trial providing ERT to a cohort of 200 menopausal women of the same ethnicities as part A. The treatment will be monitored for AD incidence once every 3 years for 15 years post-intervention. Results: Based on prior literature, we hypothesize that women of African and Latin ethnicities in Study 1 will have higher AD incidence than Caucasian and Asian women. In Study 2, we expect overall AD incidence to be lower in the ERT group than the control group. We also expect AD incidence to be higher in African and Latino participants than Caucasian and Asian participants post-ERT. Discussion: The relationship between ethnicity and AD incidence can be confounded by factors such as migratory status and the indirect relationship between racial and genetic groupings. Future studies are required to investigate these factors. Conclusion: This study will pave the path for further estrogen therapies that can reduce the risk of AD through exogenous estrogen exposure. As AD is prevalent amongst the aging population, findings will also help to reduce health disparities among postmenopausal women of multiple ethnicities.

16750 Psoriasis in racial minorities: Morphology, clinical presentation, and treatment differences

Psoriasis is a chronic inflammatory skin disease affecting 2%-3% of people worldwide. The majority of clinical data and teaching is in Caucasian ethnicities with limited data and teaching in racial minorities. We present a case series of representative psoriasis patients presenting to an urban and racially diverse hospital-based dermatology clinic in Toronto, Canada to illustrate our perspective on differences in psoriasis patients of racial minorities compared with patients of Caucasian race. Using qualitative data, we also provide selected patient quotes that support the findings and share the patient perspective.

Generational Changes in Lumbar Spinal Canal Dimensions: Findings from a Sample U.S. Population

Evaluation of lumbar canal dimensions in a Chicago population born in 2 different decades. This is a retrospective chart review analyzing computed tomography reconstruction from patients born between 1940 and 1949 (older group) and 1970 and 1979 (younger group). The cross-sectional area (CSA) and anterior-posterior diameter (APD) of the lumbar bony canal was measured at each lumbar level at the level of the pedicle. Our study includes 918 patients, 372 in the young group and 546 in the older group. Older patients have significantly larger CSA and APD at all lumbar levels compared with younger patients. Further, CSA and APD comparisons between ethnicities demonstrate significant differences between individuals of Caucasian, Asian, Hispanic, African American, and Other ethnicities. Lastly, there were no differences in CSA or APD compared with factors known to affect bone health (smoking, steroid use, osteoporosis, cancer history). As seen in European cohorts, our data suggest that patients born in the 1940s have both larger canal area and larger anterior-posterior diameter compared with the younger generation. These data suggest that significant differences exist between ethnicities. These differences highlight the importance of studying normal anatomical dimensions within different geographical populations and the importance of studying non-modifiable factors as they relate to spinal dimensions and spine patients. Furthermore, spinal canal growth seems to be negatively influenced in younger generations, a rather unexpected but worrying finding.

Abstract 2100: Deep learning can predict microsatellite instability from histology in colorectal cancer across different ethnic groups

Abstract Microsatellite instability (MSI) is known to be an important genomic marker for prediction of a patient's response to immune checkpoint inhibitors across various types of cancer. Conventional methods to measure DNA mismatch repair (MMR) status are pCR-based panel sequencing or immunohistochemical staining based methods. Recently, deep learning has been proposed as an efficient diagnostic tool in this regard, as it can learn to predict MSI directly from H&amp;E stained slides. However, it is thought that deep learning may not generalize effectively beyond the ethnicities present in the training dataset. Therefore, we investigated the impact of ethnic differences on deep learning performance at MSI classification across a range of model architectures and hyperparameters. A total of 360 WSIs from a subset of the TCGA colorectal cancer (TCGA set) and another 170 WSIs from Gangnam Severance Hospital (Yonsei University College of Medicine, Seoul, Republic of Korea, Gangnam set) were included in this study. 360 H&amp;E stained WSIs from TCGA set were divided into a set of square tiles of size 256x256um (0.5um/pixel) and then color normalized using Macenko normalization. Those tiles were divided into two classes - MSI-H and MSS (Microsatellite stable) based on the patient's MSI status. We trained various models on those tiles using a range of hyperparameters including model architecture, number of trainable layers, learning rate, and learning rate scheduling. The performance of this model was measured using the AUROC in the TCGA set (internal validation) and Gangnam set (external validation). Our results for ResNet18 - a popular convolutional network architecture - on TCGA and Gangnam test datasets are around 0.79 and 0.76 respectively, with a standard deviation on Gangnam of 0.03. Given good hyperparameters and model architecture, the model's performance on the Gangnam test data was within one standard deviation of its performance on the TCGA test data, despite the fact that said model was trained using only the TCGA data containing few asian patients. The lack of a significant performance difference challenges the notion that there are morphological differences in colorectal cancers between patients of Caucasian and Asian ethnicities that would prevent a deep learning system from generalizing effectively. Citation Format: Isaiah S. Pressman, Hongming Xu, Jeonghyun Kang, Yoon Jin Cha, Sung Hak Lee, Tae Hyun Hwang. Deep learning can predict microsatellite instability from histology in colorectal cancer across different ethnic groups [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2100.

Genetic predisposition in metabolic-dysfunction-associated fatty liver disease and cardiovascular outcomes-Systematic review.

Despite the demonstrated increased cardiovascular (CV) risk associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), genetic variants predisposing to MAFLD were not constantly associated with CV events. Recently, rs641738C>T near membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) has been studied in MAFLD and CV outcomes. Therefore, we aimed to evaluate the association between rs641738C>T in the presence and severity of hepatic steatosis, fibrosis, biochemical markers and progression to hepatocellular carcinoma (HCC), in addition to CV outcomes in MAFLD. An electronic search on PubMed, Embase and Cochrane Library for articles published till 23 March 2020 was systematically performed. Articles were screened, and data extracted from eligible studies by two reviewers independently. Studies conducted on adults with MAFLD involving European, Hispanic and African American populations evaluating rs641738 reported reduced hepatic expression of MBOAT7, increased hepatic fat content, severity of MAFLD, susceptibility to develop NASH, advanced fibrosis and HCC in adults. However, most articles involving Asian individuals contradicted these findings. Studies involving obese children associated rs641738 with increased plasma alanine aminotransferase (ALT) levels, while its association with MAFLD remains inconsistent. The rs641738 variant was assessed as a MAFLD susceptibility gene in coronary artery disease (CAD) reporting neutral effects. Despite inconclusive results in Asian populations, rs641738C>T near MBOAT7 is associated with increased hepatic fat, MAFLD severity, susceptibility to develop NASH, advanced fibrosis and HCC in adults from Caucasian, Hispanic and African American ethnicities with MAFLD, as well as elevated ALT levels in children, while exerting neutral effects in CAD.

Risk Attitudes and Digit Ratio (2D:4D): Evidence From Prospect Theory

Prenatal androgens have organizational effects on brain and endocrine system development, which may have a partial impact on economic decisions. Numerous studies investigated the relationship between prenatal testosterone and financial risk taking, yet results remain inconclusive. We suspect that this is due to difficulty in capturing risk preferences with expected utility based tasks. Prospect theory, on the other hand, suggests that risk preferences differ between gains, losses and mixed prospects, as well as for different probability levels. This study investigates the relationship between financial risk taking and 2D:4D, a putative marker of prenatal testosterone exposure, in the framework of prospect theory. We conducted our study with 350 participants from Caucasian and Asian ethnicities. We do not observe any significant relationship between 2D:4D and risk taking in neither of these domains and ethnicities.

Risk attitudes and digit ratio (2D:4D): Evidence from prospect theory

Prenatal androgens have organizational effects on brain and endocrine system development, which may have a partial impact on economic decisions. Numerous studies have investigated the relationship between prenatal testosterone and financial risk taking, yet results remain inconclusive. We suspect that this is due to difficulty in capturing risk preferences with expected utility based tasks. Prospect theory, on the other hand, suggests that risk preferences differ between gains, losses and mixed prospects, as well as for different probability levels. This study investigates the relationship between financial risk taking and 2D:4D, a putative marker of prenatal testosterone exposure, in the framework of prospect theory. We conducted our study with 350 participants of Caucasian and Asian ethnicities. We do not observe any significant relationship between 2D:4D and risk taking in either of these domains and ethnicities.