MUNSCH, Gaëlle; PROUST, Carole; LABROUCHE-COLOMER, Sylvie; AÏSSI, Dylan; BOLAND, Anne; MORANGE, Pierre-Emmanuel; ROCHE, Anne; DE CHAISEMARTIN, Luc; HARROCHE, Annie; OLASO, Robert; DELEUZE, Jean-François; JAMES, Chloe; EMMERICH, Joseph; SMADJA, David M; JACQMIN-GADDA, Helene; TREGOUET, David-Alexandre

doi:10.1093/nargab/lqad062

LABROUCHE-COLOMER, Sylvie
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

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NAR Genomics and Bioinformatics. 2023-06-28, vol. 5, n° 2, p. lqad062

Résumé en anglais

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.< Réduire

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https://oskar-bordeaux.fr/handle/20.500.12278/183815

DOI

http://dx.doi.org/10.1093/nargab/lqad062

Project ANR

University of Bordeaux Graduate School in Digital Public Health
Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease
Medical Genomics - ANR-10-LABX-0013

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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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.

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Résumé en anglais

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Unités de recherche