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Genome-wide association study of a semicontinuous trait: illustration of the impact of the modeling strategy through the study of Neutrophil Extracellular Traps levels.
LABROUCHE-COLOMER, Sylvie
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
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Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
LABROUCHE-COLOMER, Sylvie
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
< Reduce
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Language
EN
Article de revue
This item was published in
NAR Genomics and Bioinformatics. 2023-06-28, vol. 5, n° 2, p. lqad062
English Abstract
Over the last years, there has been a considerable expansion of genome-wide association studies (GWAS) for discovering biological pathways underlying pathological conditions or disease biomarkers. These GWAS are often ...Read more >
Over the last years, there has been a considerable expansion of genome-wide association studies (GWAS) for discovering biological pathways underlying pathological conditions or disease biomarkers. These GWAS are often limited to binary or quantitative traits analyzed through linear or logistic models, respectively. In some situations, the distribution of the outcome may require more complex modeling, such as when the outcome exhibits a semicontinuous distribution characterized by an excess of zero values followed by a non-negative and right-skewed distribution. We here investigate three different modeling for semicontinuous data: Tobit, Negative Binomial and Compound Poisson-Gamma. Using both simulated data and a real GWAS on Neutrophil Extracellular Traps (NETs), an emerging biomarker in immuno-thrombosis, we demonstrate that Compound Poisson-Gamma was the most robust model with respect to low allele frequencies and outliers. This model further identified the MIR155HG locus as significantly ( = 1.4 × 10) associated with NETs plasma levels in a sample of 657 participants, a locus recently highlighted to be involved in NETs formation in mice. This work highlights the importance of the modeling strategy for GWAS of a semicontinuous outcome and suggests Compound Poisson-Gamma as an elegant but neglected alternative to Negative Binomial for modeling semicontinuous outcome in the context of genomic investigations.Read less <
ANR Project
University of Bordeaux Graduate School in Digital Public Health
Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease - ANR-18-RHUS-0002
Medical Genomics - ANR-10-LABX-0013
Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease - ANR-18-RHUS-0002
Medical Genomics - ANR-10-LABX-0013