Genetic heterogeneity: Challenges, impacts, and methods through an associative lens.
GWAS
complex disease
genetic heterogeneity
precision medicine
Journal
Genetic epidemiology
ISSN: 1098-2272
Titre abrégé: Genet Epidemiol
Pays: United States
ID NLM: 8411723
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
06
07
2022
received:
18
05
2022
accepted:
19
07
2022
pubmed:
5
8
2022
medline:
19
11
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
Genetic heterogeneity describes the occurrence of the same or similar phenotypes through different genetic mechanisms in different individuals. Robustly characterizing and accounting for genetic heterogeneity is crucial to pursuing the goals of precision medicine, for discovering novel disease biomarkers, and for identifying targets for treatments. Failure to account for genetic heterogeneity may lead to missed associations and incorrect inferences. Thus, it is critical to review the impact of genetic heterogeneity on the design and analysis of population level genetic studies, aspects that are often overlooked in the literature. In this review, we first contextualize our approach to genetic heterogeneity by proposing a high-level categorization of heterogeneity into "feature," "outcome," and "associative" heterogeneity, drawing on perspectives from epidemiology and machine learning to illustrate distinctions between them. We highlight the unique nature of genetic heterogeneity as a heterogeneous pattern of association that warrants specific methodological considerations. We then focus on the challenges that preclude effective detection and characterization of genetic heterogeneity across a variety of epidemiological contexts. Finally, we discuss systems heterogeneity as an integrated approach to using genetic and other high-dimensional multi-omic data in complex disease research.
Identifiants
pubmed: 35924480
doi: 10.1002/gepi.22497
pmc: PMC9669229
mid: NIHMS1825514
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
555-571Subventions
Organisme : NIA NIH HHS
ID : R01 AG066833
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148469
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG000046
Pays : United States
Organisme : NLM NIH HHS
ID : F31 LM013583
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM012601
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM010098
Pays : United States
Informations de copyright
© 2022 The Authors. Genetic Epidemiology published by Wiley Periodicals LLC.
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