Impact of Genetic Variation on Human Disease: From Genomics to Phenotype

Xiaohui Shi

doi:10.54097/tq1bbt82

Authors

Xiaohui Shi

DOI:

https://doi.org/10.54097/tq1bbt82

Keywords:

Genetic Variation, Human Disease, Disease Susceptibility, Precision Medicine, Genetic Epidemiology

Abstract

The impact of genetic variation on human disease is a multifaceted phenomenon involving genomics, epigenetics, and phenotype relationships. Advances in human genetic analysis technology have revolutionized our understanding of genetic disorders, enabling large-scale screens to explore associations between sequence variants and disease susceptibility. Environmental stimuli also contribute to epigenetic modifications that shape gene expression and phenotypic traits. Recent research on monozygotic twins highlights the role of non-genetic factors in phenotypic differences, underscoring the complex interplay between genetics and environment. The literature review highlights seminal studies that elucidate genetic and evolutionary mechanisms underlying human disease, providing insights for personalized medicine. Methods such as pharmacogenetics and immunomics provide avenues for precision therapies and immunological research. The Heterogeneity Weighted U test and the Gaussian random effects model facilitate the exploration of phenotype-genotype relationships and help to assess genetic heterogeneity in disease models. Simulation experiments deepen our understanding of the impact of genetic variation on disease manifestation. The interdisciplinary approaches are crucial to unravel the complex genetic landscape of human diseases and to develop tailored therapeutic interventions.

Downloads

Download data is not yet available.

References

Volpato, Viola, and Caleb Webber. "Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility." Disease models & mechanisms 13, no. 1 (2020): dmm042317.

Benton, Mary Lauren, Abin Abraham, Abigail L. LaBella, Patrick Abbot, Antonis Rokas, and John A. Capra. "The influence of evolutionary history on human health and disease." Nature Reviews Genetics 22, no. 5 (2021): 269-283.

Wang, Quanli, Ryan S. Dhindsa, Keren Carss, Andrew R. Harper, Abhishek Nag, Ioanna Tachmazidou, Dimitrios Vitsios et al. "Rare variant contribution to human disease in 281,104 UK Biobank exomes." Nature 597, no. 7877 (2021): 527-532.

Frazer, Jonathan, Pascal Notin, Mafalda Dias, Aidan Gomez, Joseph K. Min, Kelly Brock, Yarin Gal, and Debora S. Marks. "Disease variant prediction with deep generative models of evolutionary data." Nature 599, no. 7883 (2021): 91-95.

Aganezov, Sergey, Stephanie M. Yan, Daniela C. Soto, Melanie Kirsche, Samantha Zarate, Pavel Avdeyev, Dylan J. Taylor et al. "A complete reference genome improves analysis of human genetic variation." Science 376, no. 6588 (2022): eabl3533.

Zhang, Yonghong, Ling Qin, Yan Zhao, Ping Zhang, Bin Xu, Kang Li, Lianchun Liang et al. "Interferon-induced transmembrane protein 3 genetic variant rs12252-C associated with disease severity in coronavirus disease 2019." The Journal of infectious diseases 222, no. 1 (2020): 34-37.

Richardson, Tom G., Eleanor Sanderson, Benjamin Elsworth, Kate Tilling, and George Davey Smith. "Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study." Bmj 369 (2020).

de Sá, Nathalia Beatriz Ramos, Nara Cristina Silva de Souza, Milena Neira-Goulart, Marcelo Ribeiro-Alves, Tatiana Pereira Da Silva, Jose Henrique Pilotto, Valeria Cavalcanti Rolla et al. "Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes." Frontiers in Cellular and Infection Microbiology 12 (2022): 962059.

Romeo, Stefano, Arun Sanyal, and Luca Valenti. "Leveraging human genetics to identify potential new treatments for fatty liver disease." Cell metabolism 31, no. 1 (2020): 35-45.

Borgo, Christian, Claudio D’Amore, Stefania Sarno, Mauro Salvi, and Maria Ruzzene. "Protein kinase CK2: a potential therapeutic target for diverse human diseases." Signal Transduction and Targeted Therapy 6, no. 1 (2021): 183.