A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study.

The Circadia Study (Circadia) is a novel "direct-to-participant" research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.

Mobile Apps for Dietary and Food Timing Assessment: Evaluation for Use in Clinical Research.

BACKGROUND: Over the last decade, health mobile apps have become an increasingly popular tool used by clinicians and researchers to track food consumption and exercise. However, many consumer apps lack the technological features for facilitating the capture of critical food timing details. OBJECTIVE: This study aimed to introduce users to 11 apps from US app stores that recorded both dietary intake and food timing to establish which one would be the most appropriate for clinical research. METHODS: To determine a viable app that recorded both dietary intake and food timing for use in a food timing-related clinical study, we evaluated the time stamp data, usability, privacy policies, the accuracy of nutrient estimates, and general features of 11 mobile apps for dietary assessment that were available on US app stores. The following apps were selected using a keyword search of related terms and reviewed: text entry apps-Cronometer, DiaryNutrition, DietDiary, FoodDiary, Macros, and MyPlate; image entry apps-FoodView and MealLogger; and text plus image entry apps-Bitesnap, myCircadianClock, and MyFitnessPal. RESULTS: Our primary goal was to identify apps that recorded food time stamps, which 8 (73%) of the 11 reviewed apps did. Of the 11 apps, only 4 (36%) allowed users to edit the time stamps. Next, we sought to evaluate the usability of the apps using the System Usability Scale across 2 days, and 82% (9/11) of the apps received favorable scores for usability. To enable use in research and clinical settings, the privacy policies of each app were systematically reviewed using common criteria, with 1 (9%) Health Insurance Portability and Accountability Act-compliant app (Cronometer). Furthermore, protected health information was collected by 9 (82%) of the 11 apps. Finally, to assess the accuracy of the nutrient estimates generated by these apps, we selected 4 sample food items and a 3-day dietary record to input into each app. The caloric and macronutrient estimates of the apps were compared with the nutrient estimates provided by a registered dietitian using the Nutrition Data System for Research database. In terms of the 3-day food record, the apps were found to consistently underestimate daily calories and macronutrients compared with the Nutrition Data System for Research output. CONCLUSIONS: Overall, we found that the Bitesnap app provided flexible dietary and food timing functionality capable of being used in research and clinical settings, whereas most other apps lacked in the necessary food timing functionality or user privacy.

Reanalysis of clinical exome identifies the second variant in two individuals with recessive disorders.

Clinical exome/genome sequencing is increasingly being utilized by clinicians to diagnose various likely genetic conditions, but many cases remain undiagnosed. In a subset of those undiagnosed cases, a single heterozygous variant in an autosomal recessive (AR) condition with consistent phenotype may be identified, raising the question if a second variant is missing. Here, we report two cases of recessive conditions in which only one heterozygous variant was initially reported by clinical exome sequencing, and on research reanalysis a second heterozygous variant in trans was identified. We performed a review of the existing exome reanalysis literature and found that this aspect is often not emphasized. These findings highlight the importance of data reanalysis in undiagnosed cases where only a single disease-associated variant is identified in an AR condition with a strong link to presenting phenotype.