Nonparametric evaluation of quantitative traits in population-based association studies when the genetic model is unknown.

PloS One
Frank KonietschkeLudwig A Hothorn

Abstract

Statistical association between a single nucleotide polymorphism (SNP) genotype and a quantitative trait in genome-wide association studies is usually assessed using a linear regression model, or, in the case of non-normally distributed trait values, using the Kruskal-Wallis test. While linear regression models assume an additive mode of inheritance via equi-distant genotype scores, Kruskal-Wallis test merely tests global differences in trait values associated with the three genotype groups. Both approaches thus exhibit suboptimal power when the underlying inheritance mode is dominant or recessive. Furthermore, these tests do not perform well in the common situations when only a few trait values are available in a rare genotype category (disbalance), or when the values associated with the three genotype categories exhibit unequal variance (variance heterogeneity). We propose a maximum test based on Marcus-type multiple contrast test for relative effect sizes. This test allows model-specific testing of either dominant, additive or recessive mode of inheritance, and it is robust against variance heterogeneity. We show how to obtain mode-specific simultaneous confidence intervals for the relative effect sizes to aid in interpretin...Continue Reading

References

Mar 1, 1995·Genetics·L Kruglyak, E S Lander
Mar 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bert GoldKenneth Offit
Aug 21, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Ayman H FanousKenneth S Kendler
Oct 22, 2008·Biometrical Journal. Biometrische Zeitschrift·Mario Hasler, Ludwig A Hothorn
Nov 1, 1994·TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·W R Wu, W M Li

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Citations

Oct 18, 2015·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Urs HeilbronnerThomas G Schulze
Aug 2, 2013·The International Journal of Biostatistics·Frank KonietschkeLudwig A Hothorn
Aug 7, 2017·NPJ Genomic Medicine·Lenha MobuchonMarc-Henri Stern

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Software Mentioned

R
PLINK
R library
nparcomp

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