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Supplementary Material for: When Is an Endophenotype Useful to Detect Association to a Disease? Exploring the Relationships between Disease Status, Endophenotype and Genetic Polymorphisms
Version 2 2016-07-29, 09:55Version 2 2016-07-29, 09:55
Version 1 2016-07-29, 09:44Version 1 2016-07-29, 09:44
journal contribution
posted on 2016-07-29, 09:55authored byBureau A., Croteau J.
Objectives: To investigate the conditions and analysis strategies
required so that endophenotypes related to a disease
help discover genetic variants involved in the disease. Methods:
The association with disease susceptibility variants is
examined as a function of the relationships between disease
status, endophenotype values and the genotype at another
disease or endophenotype susceptibility locus assumed to
be previously known, using approximate linear models of allele
frequencies as a function of these variables and simulations
in the context of family studies when the endophenotype
is dichotomous. Results: Under genetic mechanisms
where the risk allele of the tested locus has an effect exclusively
in subjects with the endophenotype, the risk allele frequency
differences between affected and unaffected subjects
are much greater in the subset of subjects with an endophenotype
impairment than in those without such an
impairment, and power gains are obtained when testing the
association under a joint disease-endophenotype model, both with two-locus or single-locus tests. However, with
moderate main effect on the risk of disease or endophenotype
impairment, testing directly the association between
risk allele and disease or endophenotype is more powerful
than testing under a joint disease-endophenotype model.
Conclusions: Joint modeling of disease and endophenotype
should be used only in parallel with standard disease association
testing.