IMPORTANCEAlthough rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic variation also contributes to the cause of AF in those of minority ethnicity.OBJECTIVES To assess the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset AF and determine genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTSIn this cohort, family-based study, probands of African and Hispanic descent with early-onset AF (defined as AF occurring in individuals aged Յ66 years) prospectively enrolled in a clinical and genetic biorepository underwent sequencing of 60 candidate genes.

Atrial fibrillation (AF) is the most prevalent cardiac rhythm disorder worldwide but the underlying genetic and molecular mechanisms and the response to therapies is not fully understood. Despite a greater burden of AF risk factors in Hispanics/Latinos the prevalence of AF remains low. Over the last decade, genome-wide association studies have identified numerous AF susceptibility loci in mostly whites of European descent. The goal of this study was to determine if the top 9 single nucleotide polymorphisms (SNPs) associated with AF in patients of European descent also increase susceptibility to AF in Hispanics/Latinos. AF cases were prospectively enrolled in the University of Illinois at Chicago (UIC) AF Registry and control subjects were identified from the UIC Cohort of Patients, Family and Friends. AF cases and controls were genotyped for 9 AF risk SNPs at chromosome 1q21: rs13376333, rs6666258; chr1q24: rs3903239; chr4q25: rs2200733; rs10033464; chr10q22: rs10824026; chr14q23: rs1152591; chr16q22: rs2106261 and rs7193343. The study sample consisted of 713 Hispanic/Latino subjects including 103 AF cases and 610 controls. Among the 8 AF risk SNPs genotyped, only rs10033464 SNP at chromosome (chr) 4q25 (near PITX2) was significantly associated with development of AF after multiple risk factor adjustment and multiple testing (adj. odds ratio [OR] 2.27, 95% confidence interval [CI] 1.31–3.94; P = 3.3 x 10−3). Furthermore, the association remained significant when the analysis was restricted to Hispanics of Mexican descent (adj. OR 2.32, 95% CI 1.35–3.99; P = 0.002. We confirm for the first time the association between a chromosome 4q25 SNP and increased susceptibility to AF in Hispanics/Latinos. While the underlying molecular mechanisms by which the chr4q25 SNP modulates AF risk remains unclear, this study supports a genetic basis for non-familial AF in patients of Hispanic descent.

Key Points Question What is the association of family history with the pathogenesis of early-onset atrial fibrillation in patients of African, European, and Hispanic descent? Findings In this cohort study of 664 patients, probands with early-onset atrial fibrillation were significantly more likely to have a family history of arrhythmia in first-degree relatives than patients with non–early-onset atrial fibrillation. Compared with European American probands, African American and Hispanic/Latino probands with early-onset atrial fibrillation were more likely to have a first-degree relative with arrhythmia. Meaning These findings support genetic predisposition to early-onset atrial fibrillation across individuals of European, African, and Hispanic/Latino descent and have important implications for identifying family members at risk for atrial fibrillation and sequencing candidate genes.

Introduction Access to safe termination of pregnancy (TOP) is an essential component of women's health care, but relies on adequate numbers of trained providers. It is therefore important that the extent and quality of abortion teaching in the undergraduate medical curricula in the UK is assessed. The study aimed to reflect upon UK medical students' experiences of and attitudes towards TOP teaching in their medical curricula, in order to identify both successes and shortcomings in the current provision of undergraduate medical education on TOP. Methods Medical students studying at institutions within the UK were invited to complete an online questionnaire, which was available for responses over a 4-month period from May to August 2015. The study used a 36-item questionnaire, with a mixture of binary, sliding-scale, categorical and free-text response items. Participants were recruited via the social media platforms of Medsin-UK, a student-led global health charity. Results The survey received 119 responses from participants studying in 21 universities, representing all stages of the medical course. 53% of those surveyed had not received any pre-clinical teaching, while 78% had not received any formal clinical teaching on TOP. The majority of students would have liked more teaching on TOP as part of their medical curriculum: 73% reported wanting more lecture-based/classroom-based teaching and 59% reported wanting more clinical exposure to TOP. All respondents were asked how sufficient they felt their pre-clinical and clinical teaching on TOP had been on a 1-10 scale; 71% gave a sufficiency score of 3 or less. 81% of respondents said that they would not be comfortable counselling a woman about her options for a pregnancy. 84% put this down to a lack of knowledge, and 52% cited a lack of confidence in appropriate communication skills. Only 7.1% associated it with a personal objection to TOP. When asked on a 1-10 scale how relevant they felt teaching on abortion was to medical students today, 45% answered with '10' -'very relevant'. Conclusion We identified dissatisfaction with TOP education and a lack of confidence in TOP-related clinical skills in our participants. Such results indicate the need for further scrutiny of the content and quality of teaching on TOP in the medical curriculum. An improvement in delivery of undergraduate medical education on TOP is necessary to ensure that junior doctors are confident in their abilities to provide competent and compassionate care to women seeking TOP. FC2.003One Trust's struggle to reduce its stillbirth rate. A financial assessment of implementing 3 weekly growth scanning for women at risk of fetal growth restriction Sagar, R; Arlidge, M; Hayman, R Gloucester Royal Hospital, Gloucestershire, UK Introduction Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality. The UK has one of the highest stillbirth rates in Europe. Confidential enquiries have demonstrated that most stillbirths due to FGR are potentially avoidable. Reducing stillbi...

Introduction Mutations in cardiac ion channels, structural proteins and signaling molecules have been identified in European whites with early-onset AF (EOAF). However, it remains unclear if genetic variation also contributes to the etiology of EOAF in ethnic minorities. Purpose To determine the prevalence of disease causing variants in candidate AF genes in African American and Hispanic/Latino probands with EOAF. Method In this family-based study, probands of African and Hispanic descent with EOAF (defined as AF ≤65 years) were prospectively enrolled in a clinical-DNA biorepository and underwent targeted sequencing for 60 AF candidate genes. Variants were filtered at 20X read depth and clinically evaluated with American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) as well as the Association for Clinical Genomic Science (ACGS) criteria for disease-causing mutations. Results Among 227 EOAF probands with mean (SD) age of AF 51.0 (9.9) years, 132 (58.0%) were men and 148 (65.0%) African American and 79 (35.0%) Hispanic/Latino. Sequencing 60 candidate AF genes revealed 90 variants that met filtering criteria and underwent clinical evaluation. We identified 16 (7.0%) EOAF probands with a likely pathogenic or pathogenic variant with the majority being loss of function (62.5%) and located in the TTN gene (50.0%). We confirmed a family history of AF in 24 probands (10.6%) and 6 families with >1 affected member a variant of unknown significance (VUS) in genes encoding for a sodium channel (SCN10A), potassium channel (KCNE5), sarcomeric proteins (MYH6, TTN) and atrial natriuretic peptide (NPPA) co-segregated with AF. Conclusion Gene sequencing in African American and Hispanic/Latinos probands with EOAF identified a small percentage of disease causing variants in patients with EOAF. Our findings not only represent important progress toward molecular phenotyping of EOAF, but also provides insight into the underlying pathophysiology toward targeted mechanism-based therapies for AF in ethnic minorities. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): American Heart Association