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Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.

AbstractPurposeMethodsResultsDiscussionTraumatic experiences are ubiquitous and associated with negative impacts on health and wellbeing in patients, students, and clinicians. Trauma-informed care (TIC) is a harm reduction framework that aims to minimize re-traumatization and the negative health impacts of trauma. TIC is increasingly being incorporated into undergraduate medical education (UME) curricula; however, to date, there is no standardized curriculum to support faculty in precepting TIC clinical skills.We created a series of five educational modules in an asynchronous online format to support faculty in the instruction and precepting of TIC clinical skills in UME. The modules instruct on trauma epidemiology, trauma-informed clinical skills, trauma-informed precepting, and trauma-informed self-care (TISC). The modules are interactive and utilize multimedia content.Fifty-three faculty members of the primary care clerkship participated in the modules. After the modules, faculty demonstrated increased knowledge of TIC, though their comfort in applying principles with patients and students was unchanged.We present a novel, standardized curriculum to support faculty in the practice and precepting of TIC clinical skills. The intervention is shown to promote knowledge surrounding TIC. In the future, pairing these asynchronous modules with in-person training may be necessary to improve comfort with the application of these skills. [ABSTRACT FROM AUTHOR]