Detecting heritable phenotypes without a model using fast permutation testing for heritability and set-tests

Schweiger, Regev; Fisher, Eyal; Weissbrod, Omer; Rahmani, Elior; Müller-Nurasyid, Martina; Kunze, Sonja; Gieger, Christian; Waldenberger, Melanie; Rosset, Saharon und Halperin, Eran (2018): Detecting heritable phenotypes without a model using fast permutation testing for heritability and set-tests. In: Nature Communications, Bd. 9, 4919

Abstract

Testing for association between a set of genetic markers and a phenotype is a fundamental task in genetic studies. Standard approaches for heritability and set testing strongly rely on parametric models that make specific assumptions regarding phenotypic variability. Here, we show that resulting p-values may be inflated by up to 15 orders of magnitude, in a heritability study of methylation measurements, and in a heritability and expression quantitative trait loci analysis of gene expression profiles. We propose FEATHER, a method for fast permutation-based testing of marker sets and of heritability, which properly controls for false-positive results. FEATHER eliminated 47% of methylation sites found to be heritable by the parametric test, suggesting a substantial inflation of false-positive findings by alternative methods. Our approach can rapidly identify heritable phenotypes out of millions of phenotypes acquired via high-throughput technologies, does not suffer from model misspecification and is highly efficient.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2041-1723
• Sprache: Englisch