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Use of Electronic Health Records, Disease Registries, and Health Insurance Databases in Ophthalmology
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Rachel Marjorie Wei Wen Tseng, Grace May Chuang, Zhi Da Soh, Yih-Chung Tham
Aside from replicating genetic findings, the integration of EHR and genomics also led to the development of a technique known as phenome-wide association study (PheWAS). Compared to GWAS, which consists solely of identifying the association between genetic variants and a phenotype, PheWAS simultaneously searches for associations between clinical phenotypes and a given genetic variant and can identify pleiotropy (22, 23). In addition, inputs other than SNPs are being explored. These include a set of SNPs, disease exposure, drug exposure, transcription factor-based motifs, or other functional annotation data, thereby expanding the functions of PheWAS in EHR-based research (24, 25). PheWAS is often used as an approach complementary to GWAS, and the integration of these two tools has been explored in EHR-related research to validate findings, replicate known associations, identify pleiotropy, and predict disease development (26).
The Host Immune Response Against Parasitic Helminth Infection
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
While humoral responses have been considered the hallmark of an effective immune reaction, there is considerable evidence that protective immunity is not mediated by antibodies alone. Thus, passive transfer of antibody in experimental systems (including schistosomiasis, intestinal helminth infections, and filariasis) has not been able to completely protect against challenge infection. Indeed, in helminth infections, antibodies must act in concert with cellular components of the immune network in order to eliminate these parasites. For example, the in vitro killing of schistosomula does not occur in the presence of antischistosome antibody alone; instead it requires the presence of either complement (125) or effector cells such as eosinophils (87), neutrophils (126), macrophages (127), monocytes (128), mast cells (115), or platelets (129). Neither is this phenome-non limited to schistosomes, as microfilariae have also been shown to require effector cells along with specific antibodies.
Whole exome and whole genome sequencing
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Other considerations in variant annotation include the strength of an association of the variant with the disease and with the phenotype of the patient; the possibility of phenotypic heterogeneity must always be considered. In addition to the clinical databases discussed previously, a number of other matching databases, such as Gene-Matcher (https://genematcher.org/), DECIPHER (https://decipher.sanger.ac.uk/), and Phenome-Central (https://www.phenomecentral.org/), can help to identify matching cases with the use of de-identified data, such as gene names or disease features. These tools are publicly available and do not require computational expertise.
Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence
Published in Canadian Journal of Pain, 2022
Adam J. Dourson, Adam Willits, Namrata G.R. Raut, Leena Kader, Erin Young, Michael P. Jankowski, Vidya Chidambaran
Because single variants account only for small effect sizes and different pathways play concomitant roles in CPSP development, one must consider the combined effect of several gene variants (polygenic risk) in CPSP.17 Polygenic risk scores (PRSs)—the sum of weighted effects of different phenotype-associated alleles—have been shown to predict several complex conditions.185–187 An atlas of PRS associations and putative causal relationships across the human phenome was reported, though it did not include CPSP as a phenotype.188 Chidambaran et al. recently combined systems biology and penalized regression techniques to determine PRS, which improved prediction of CPSP risk compared to nongenetic models.189 Another recent study determined a PRS that suggested significant overlap of genetics of CPSP with chronic widespread pain, rheumatoid arthritis, and sciatica (but not with chronic headache and migraine). They suggested that this overlap is potentially due to common mechanisms regulating neurological signaling (sodium channels) and inflammatory response.190 Interestingly, this overlap was nullified in the replication cohort when subjects were randomly reassigned. Thus, further research is needed to enumerate polygenic risk for therapeutic targeting.191,192
Linking endotypes to omics profiles in difficult-to-control asthma using the diagnostic Chinese medicine syndrome differentiation algorithm
Published in Journal of Asthma, 2020
Wenping Song, Si Zheng, Meng Li, Xia Zhang, Rui Cao, Cheng Ye, Rongguang Shao, Guangxi Li, Jiao Li, Shigang Liu, Hui Li, Liang Li
Our study employed a highly similar idea to a recently developed approach, PheWAS (phenome-wide association study), an alternative methodology to understand etiologies of complex diseases and to compensate or provide solutions for a variety of limited factors in GWAS. PheWAS usually investigate associations of a genotype with a wide spectrum of human phenotypes, namely the phenome. With this phenotype-to-genotype approach, many phenotypes of previously unappreciated etiologies in comprehensive diseases have been linked to some genes/pathways [27]. Although some researchers have made progress in endotypic classification of patients with asthma, most studies have only focused on airway inflammation, thereby ignoring the holistic nature of the human body. In contrast, our CMSDA classification approach focuses not only on known symptoms, like allergy, inflammation, or other asthma-associated symptoms, but also on unknown systematic phenotypes [28,29]. Therefore, the CMSDA could help identify more phenotypes not yet shown to be associated with asthma-related genes or asthma in general. The combined examination of local airway response and systematic evaluation of the human body could be more intuitive and helpful in future PheWAS. Moreover, this approach might provide new insights regarding this disease, in order to develop methodologies that define diverse phenotypes and enhance PheWAS practicality [30–32]. Certainly, more precise PheWAS stratification would be obtained by this approach in the future, to define the phenome using electronic medical records for larger sample size.
Toward a phenomic analysis of chronic postsurgical pain following cardiac surgery
Published in Canadian Journal of Pain, 2019
Hance Clarke, Ajit Rai, James Bao, Michael Poon, Vivek Rao, George Djaiani, Scott Beattie, Gabrielle Page, Manon Choiniere, Michael McGillion, Monica Parry, Judith Hunter, Judy Watt-Watson, Loren Martin, Liza Grosman-Rimon, Dinesh Kumbhare, John Hanlon, Ze’ev Seltzer, Joel Katz
Third, this raises the question of how to identify the best intermediate phenomes. In the present study, we addressed this issue by first using clinical parameters of CPSP to classify patients as having/not having CPSP and then using this grouping strategy to survey potential phenomes and intermediate phenomes that could be used for genetic association. However, the final test of how effective a CPSP-related phenotype is as a phenome can only be made if the genetic association analysis identifies genetic polymorphisms of relevance to CPSP and the effect size of carrying these polymorphisms can explain a sizable portion of the heritable, allelic risk for CPSP. Thus, to assess the effectiveness of a phenome necessitates having genotypic data of a sufficiently statistically powered cohort of patients with CPSP.