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In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series of genome-wide association studies (GWASs) for low-density lipoprotein cholesterol (LDL-C) response to statin therapy in 34,874 participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort as a case study to investigate the impact of baseline adjustment on results generated from pharmacogenomic studies of quantitative change. Across phenotypes of statin-induced LDL-C change, baseline adjustment identified variants from six loci meeting genome-wide significance (, and /). In contrast, baseline-unadjusted analyses yielded variants from three loci meeting the criteria for genome-wide significance (, , and ). A genome-wide heterogeneity test of baseline versus statin on-treatment LDL-C levels was performed as the definitive test for the true effect of genetic variants on statin-induced LDL-C change. These findings were generally consistent with the models not adjusting for baseline signifying that genome-wide significant hits generated only from baseline-adjusted analyses (/) were likely biased. We then comprehensively reviewed published GWASs of drug-induced quantitative change and discovered that more than half (59%) inappropriately adjusted for baseline. Altogether, we demonstrate that (1) baseline adjustment introduces bias in pharmacogenomic studies of quantitative change and (2) this erroneous methodology is highly prevalent. We conclude that it is critical to avoid this common statistical approach in future pharmacogenomic studies of quantitative change.
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http://dx.doi.org/10.1038/s41525-019-0109-4 | DOI Listing |
J Orthop Surg Res
December 2024
Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City, Liaoning Province, 110004, China.
Background: The muscles that encase the hip serve a crucial role in both joint stability and functional efficacy, and as developmental dysplasia of the hip (DDH) progresses, the surrounding musculature may undergo specific adaptations that reduce joint stability, thereby exacerbating dislocation. Yet, the exact nature of changes in muscle morphology and quality remains inadequately investigated. This study aimed to compare magnetic resonance imaging (MRI) evaluations of the iliopsoas and other hip flexor and extensor muscles in children with unilateral DDH before and after treatment.
View Article and Find Full Text PDFBMJ Open
December 2024
Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
Introduction: Trachoma is caused by the bacterium (). The WHO recommends the SAFE strategy for trachoma elimination: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Multiple rounds of SAFE implementation have proven insufficient to eliminate trachoma in Ethiopia, where over 50% of the global trachoma burden remains.
View Article and Find Full Text PDFBMJ Open
December 2024
Department of Primary Care and Public Health, School of Public Health, Imperial College London Faculty of Medicine, London, UK
Objectives: We sought to review studies that examine healthcare professionals' and students' knowledge, attitudes and practices (KAP) regarding medication disposal. We also explore recommendations and barriers related to appropriate medication disposal.
Design: A systematic review was conducted that adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Toxicol Appl Pharmacol
December 2024
Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address:
Background: The clinical efficacies of Ulcerative colitis (UC) are far from satisfactory. Fucoxanthin (FUC) is a marine carotenoid that is abundant in seaweed and microalgae. It has been reported that FUC can possess anti-inflammatory and antioxidant.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Biol Lipids
December 2024
Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Aging and Disease, Nanchang, Jiangxi, China. Electronic address:
Sphingolipids are crucial components of cell membranes and serve as important signaling molecules. Ceramide, as the central hub of sphingolipid metabolism, plays a significant role in various biological processes, including the cell cycle, apoptosis, and cellular aging. Alterations in sphingolipid metabolism are implicated in cellular aging, however, the specific sphingolipid components and intrinsic mechanisms that mediate this process remain largely uncharacterized.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!