A Comparison of Different Approaches to Clinical Phenotyping of Lithium Response: A Proof of Principle Study Employing Genetic Variants of Three Candidate Circadian Genes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Pharmaceuticals Année : 2021

A Comparison of Different Approaches to Clinical Phenotyping of Lithium Response: A Proof of Principle Study Employing Genetic Variants of Three Candidate Circadian Genes

Résumé

Optimal classification of the response to lithium (Li) is crucial in genetic and biomarker research. This proof of concept study aims at exploring whether different approaches to phenotyping the response to Li may influence the likelihood of detecting associations between the response and genetic markers. We operationalized Li response phenotypes using the Retrospective Assessment of Response to Lithium Scale (i.e., the Alda scale) in a sample of 164 cases with bipolar disorder (BD). Three phenotypes were defined using the established approaches, whilst two phenotypes were generated by machine learning algorithms. We examined whether these five different Li response phenotypes showed different levels of statistically significant associations with polymorphisms of three candidate circadian genes (RORA, TIMELESS and PPARGC1A), which were selected for this study because they were plausibly linked with the response to Li. The three original and two revised Alda ratings showed low levels of discordance (misclassification rates: 8–12%). However, the significance of associations with circadian genes differed when examining previously recommended categorical and continuous phenotypes versus machine-learning derived phenotypes. Findings using machine learning approaches identified more putative signals of the Li response. Established approaches to Li response phenotyping are easy to use but may lead to a significant loss of data (excluding partial responders) due to recent attempts to improve the reliability of the original rating system. While machine learning approaches require additional modeling to generate Li response phenotypes, they may offer a more nuanced approach, which, in turn, would enhance the probability of identifying significant signals in genetic studies.
Fichier principal
Vignette du fichier
Scott et al 2021 pharmaceuticals.pdf (664.17 Ko) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03568955 , version 1 (07-10-2022)

Identifiants

Citer

Jan Scott, Mohamed Lajnef, Romain Icick, Frank Bellivier, Cynthia Marie-Claire, et al.. A Comparison of Different Approaches to Clinical Phenotyping of Lithium Response: A Proof of Principle Study Employing Genetic Variants of Three Candidate Circadian Genes. Pharmaceuticals, 2021, 14 (11), pp.1072. ⟨10.3390/ph14111072⟩. ⟨hal-03568955⟩
21 Consultations
20 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More