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- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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- Dixit, K, et al.
(författare)
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Barriers and facilitators to accessing tuberculosis care in Nepal: a qualitative study to inform the design of a socioeconomic support intervention
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:10, s. e049900-
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Tidskriftsartikel (refereegranskat)abstract
- Psychosocial and economic (socioeconomic) barriers, including poverty, stigma and catastrophic costs, impede access to tuberculosis (TB) services in low-income countries. We aimed to characterise the socioeconomic barriers and facilitators of accessing TB services in Nepal to inform the design of a locally appropriate socioeconomic support intervention for TB-affected households.DesignFrom August 2018 to July 2019, we conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) with purposively selected multisectoral stakeholders. The data were managed in NVivo V.12, coded by consensus and analysed thematically.SettingThe study was conducted in four districts, Makwanpur, Chitwan, Dhanusha and Mahottari, which have a high prevalence of poverty and TB.ParticipantsSeven FGDs were conducted with 54 in-country stakeholders, grouped by stakeholders, including people with TB (n=21), community stakeholders (n=13) and multidisciplinary TB healthcare professionals (n=20) from the National TB Programme.ResultsThe perceived socioeconomic barriers to accessing TB services were: inadequate TB knowledge and advocacy; high food and transportation costs; income loss and stigma. The perceived facilitators to accessing TB care and services were: enhanced championing and awareness-raising about TB and TB services; social protection including health insurance; cash, vouchers and/or nutritional allowance to cover food and travel costs; and psychosocial support and counselling integrated with existing adherence counselling from the National TB Programme.ConclusionThese results suggest that support interventions that integrate TB education, psychosocial counselling and expand on existing cash transfer schemes would be locally appropriate and could address the socioeconomic barriers to accessing and engaging with TB services faced by TB-affected households in Nepal. The findings have been used to inform the design of a socioeconomic support intervention for TB-affected households. The acceptability, feasibility and impact of this intervention on TB-related costs, stigma and TB treatment outcomes, is now being evaluated in a pilot implementation study in Nepal.
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| 7. |
- Codlin, AJ, et al.
(författare)
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Independent evaluation of 12 artificial intelligence solutions for the detection of tuberculosis
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 23895-
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Tidskriftsartikel (refereegranskat)abstract
- There have been few independent evaluations of computer-aided detection (CAD) software for tuberculosis (TB) screening, despite the rapidly expanding array of available CAD solutions. We developed a test library of chest X-ray (CXR) images which was blindly re-read by two TB clinicians with different levels of experience and then processed by 12 CAD software solutions. Using Xpert MTB/RIF results as the reference standard, we compared the performance characteristics of each CAD software against both an Expert and Intermediate Reader, using cut-off thresholds which were selected to match the sensitivity of each human reader. Six CAD systems performed on par with the Expert Reader (Qure.ai, DeepTek, Delft Imaging, JF Healthcare, OXIPIT, and Lunit) and one additional software (Infervision) performed on par with the Intermediate Reader only. Qure.ai, Delft Imaging and Lunit were the only software to perform significantly better than the Intermediate Reader. The majority of these CAD software showed significantly lower performance among participants with a past history of TB. The radiography equipment used to capture the CXR image was also shown to affect performance for some CAD software. TB program implementers now have a wide selection of quality CAD software solutions to utilize in their CXR screening initiatives.
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