Clinical response to therapeutic treatments often varies among individual patients, ranging from beneficial effect to even fatal adverse reaction. Pharmacogenomics holds the promise of personalized medicine through elucidating genetic determinants responsible for pharmacological outcomes (e.g., cytotoxicities to anticancer drugs) and therefore guide the prescription decision prior to drug treatment. Besides traditional candidate gene-based approaches, technical advances have begun to allow application of whole-genome approaches to pharmacogenomic discovery. In particular, comprehensive understanding of human genetic variation provides the basis for applying GWAS (genome-wide association studies) in pharmacogenomic research to identify genomic loci associated with pharmacological phenotypes (e.g., individual dose requirement for warfarin). We therefore briefly reviewed the background for pharmacogenetic/pharmacogenomic research with statins and warfarin as examples for the GWAS discovery and their clinical implementation. In conclusion, with some challenges, whole-genome approaches such as GWAS have allowed unprecedented progress in identifying genetic variants associated with pharmacological phenotypes, as well as provided foundation for the next wave of pharmacogenomic discovery utilizing sequencing-based approaches. Furthermore, investigation of the complex interactions among genetic and epigenetic factors on the whole-genome scale will become the post-GWAS research focus for pharmacologic complex traits.
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http://dx.doi.org/10.1002/wsbm.1199 | DOI Listing |
JCO Precis Oncol
January 2025
Medical Research Service, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN.
Purpose: Considerable genetic heterogeneity is currently thought to underlie hereditary prostate cancer (HPC). Most families meeting criteria for HPC cannot be attributed to currently known pathogenic variants.
Methods: To discover pathogenic variants predisposing to prostate cancer, we conducted a familial case-control association study using both genome-wide single-allele and identity-by-descent analytic approaches.
G3 (Bethesda)
January 2025
Canine Genetics Centre, Department of Veterinary Medicine, University of Cambridge, Cambridgeshire, CB3 0ES, UK.
Retinopathy with Vitamin E Deficiency (RVED) is a familial disease in the English Cocker Spaniel (ECS) dog breed. Ophthalmic abnormalities observed in RVED-affected ECS include lipofuscin granule deposition within the tapetal fundus and subsequent retinal degeneration resulting in visual deficits. Affected dogs may also exhibit neurological signs that include ataxia and hindlimb proprioceptive deficit.
View Article and Find Full Text PDFAnnu Rev Entomol
January 2025
Department of Entomology, China Agricultural University, Beijing, China; email:
Thanks to the fast development of sequencing techniques and bioinformatics tools, sequencing the genome of an insect species for specific research purposes has become an increasingly popular practice. Insect genomes not only provide sets of gene sequences but also represent a change in focus from reductionism to systemic biology in the field of entomology. Using insect genomes, researchers are able to identify and study the functions of all members of a gene family, pathway, or gene network associated with a trait of interest.
View Article and Find Full Text PDFPlanta
January 2025
Department of Plant Sciences, University of the Free State, Bloemfontein, South Africa.
Sorghum kernel composition is a crucial characteristic that determines its functional qualities. The total protein content of sorghum grain increases under drought stress, but starch, protein digestibility, and micronutrient contents decrease. Sorghum (Sorghum bicolor L.
View Article and Find Full Text PDFPlant Cell
December 2024
Shenzhen Research Institute, State Key Laboratory for Crop Stress Resistance and High-Efficiency Production/Shaanxi Key Laboratory of Apple, College of Horticulture, Northwest A&F University, Yangling 712100, China.
A complex regulatory network governs fruit ripening, but natural variations and functional differentiation of fruit ripening genes remain largely unknown. Utilizing a genome-wide association study (GWAS), we identified the NAC family transcription factor MdNAC18.1, whose expression is closely associated with fruit ripening in apple (Malus × domestica Borkh.
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