Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Abstract 13645: Contemporary Propensity-Matched Analysis Reveals Alarmingly High Risk Of Mortality, Arrhythmia And Cardiac Arrest In Nationwide Hospitalizations Of Patients With Heart Failure With Preserved Ejection Fraction And Cannabis Use Disorder

Background: Preliminary reports have suggested a link between cannabis use and heart failure (HF); however, with inconclusive literature on the subject, there exists an unmet need for contemporary data on outcomes of HF patients with cannabis use. The rising prevalence of Heart Failure with Preserved Ejection Fraction (HFpEF) incited us to assess the impact of cannabis use disorder (CUD) on in-hospital outcomes of HFpEF using nationwide multicenter data. Methods: Adult admissions related to HFpEF with vs. without CUD were identified using the National Inpatient Sample (Oct 2015-Dec 2017). Demographically matched cohorts, HFpEF-CUD+ vs. HFpEF-CUD-, were obtained and compared for comorbidities and in-hospital outcomes. Multivariable regression analyses were performed after controlling for confounders (demographic/hospital characteristics, comorbidities and substance abuse) to assess the risk of adverse outcomes including all-cause mortality, arrhythmia (atrial fibrillation/flutter, ventricular arrhythmia &amp; cardiac arrest) and stroke. Results: Of 3,835,473 HFpEF-related admissions, 10980 (0.3%) patients were cannabis users. Matched cohorts, CUD+ and CUD- were comparable for demographics (median age 55 vs. 54 years, &gt;60% male, &gt;80% white/black). The CUD+ cohort had a lower rate of comorbidities including hypertension (87.5% vs 88.5%), diabetes (33.7% vs 43.7%), hyperlipidemia (38.4% vs 42.1%), obesity (26.7% vs 36.2%), and renal failure (32.8% vs 39.8%) (Table 1). Despite a lower comorbidity burden, the CUD+ cohort was often admitted non-electively (95.2% vs. 92.8%) and had considerably higher odds of all-cause mortality (aOR 2.24, 95%CI:1.81-2.78), arrhythmia (aOR 1.15, 95%CI:1.05-1.25) and cardiac arrest (aOR 3.87, 95%CI: 2.88-5.21) (p&lt;0.05) (Fig. 1). Conclusions: This nationwide multicenter analysis revealed HFpEF admissions in patients with CUD had a significantly higher risk of adverse in-hospital outcomes despite a lower CVD risk. </jats:p

Abstract 13627: Increasing Trend of Cannabis Use Disorder Among Young Patients Admitted Due to Acute Myocardial Infarction

Introduction: The prevalence of cannabis use disorder (CUD) has increased in the US especially following its legalization in various states. Few studies have reported that CUD has been associated with increased Acute Myocardial Infarction (AMI) especially in the younger population. There are limited epidemiological studies that estimate the recent trend of AMI among young patients with CUD. Hypothesis: To estimate the hospitalization trends of AMI with concurrent CUD and characteristics associated with it in the young population. Methods: Study cohort was derived from the National Inpatient Sample (NIS) for the years 2007-2018. Hospitalizations due to AMI among the age group of 18-49 and concurrent CUD were identified using previously validated ICD-9-CM/ICD-10-CM. We then utilized the Cochran Armitage trend test and multivariable survey logistic regression modeling to analyze temporal trends and predictors of CUD among AMI patients. Results: Out of a total 819,354 hospitalizations due to AMI among the age group of 18-49 years, 33,488 (4.1%) had concurrent CUD. Hospitalizations due to AMI with concurrent CUD increased from 1722 (2.4%) in 2007 to 4455 (6.7%) in 2018 with a 12% yearly rate (OR 1.1; 95%CI 1.1-1.1; p&lt;0.01). AMI patients with CUD were younger (20.2% vs 7.3%; p&lt;0.01), male (78.1.2% vs 71.6%; p&lt;0.01) and African American (35.2% vs 15.8%; p&lt;0.01). In multivariable regression analysis, age 18-34 (OR 2.9; 95% CI 2.7 - 3.1; P&lt;0.01), male (OR 1.5; 95%CI 1.4 - 1.6; p&lt;0.01), African American (OR 2.5; 95% CI 2.4-2.7, p&lt;0.01), Lower socio-economic status (OR 1.3; 95% CI 1.1-1.4, p&lt;0.01), West region (OR 1.3; 95% CI 1.2-1.5, p&lt;0.01), depression (OR 1.2; 95% CI 1.1-1.3, p &lt;0.01), alcoholism were associated with higher odds of CUD and AMI. Moreover, AMI patients with CUD were more likely to be admitted during the weekend (OR 1.1; CI 1.1-1.1, p &lt;0.01). Conclusions: Our study highlights the increasing trend of AMI hospitalizations with concurrent CUD. Our study also identifies that 18-34 years of age, male gender, African American and psychiatric conditions were significant determinants of CUD in young AMI patients. This warrants additional research to prove causal association between CUD and AMI in the young population in the era of increased cannabis legalization. </jats:p