TY - JOUR
T1 - Polyunphased
T2 - An extension to polytomous outcomes of the Unphased package for family-based genetic association analysis
AU - Bureau, Alexandre
AU - Croteau, Jordie
N1 - Funding Information:
This work has been supported by the Canadian Institutes of Health research (CIHR, grant MOP-106448). We thank M. Maziade (U Laval) for access to the data from the Eastern Quebec Schizophrenia and Bipolar Disorder Study, funded by CIHR (grants MOP-74430, MOP-119408 and MOP-114988) and by a Canada Research Chair (950-200810) in the genetics of neuropsychiatric disorders of which M. Maziade is the Chair.
Publisher Copyright:
© 2017 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Polytomous phenotypes arise when a disease has multiple subtypes or when two dichotomous phenotypes are analyzed simultaneously. Few software programs offer the option to analyze such phenotypes in family studies, and none implements conditional polytomous logistic regression for within-family analysis robust to population stratification. We introduce Polyunphased, an extension to polytomous phenotypes of the Unphased package, a flexible software tool for genetic association analysis in nuclear families. Like Unphased, Polyunphased is written in C++ and runs from the command line or from a Java graphical user interface. Most Unphased options remain available in Polyunphased, including those handling missing parental genotypes while preserving robustness to population stratification, and the modelling options. Simulation studies confirmed the expected statistical behaviour of the maximum likelihood estimates of the association parameters of the conditional logistic regression model when the corresponding association parameters in the parental term of the likelihood function are set to 0, but revealed convergence problems when estimating these parental association parameters separately. The former approach is thus recommended with polytomous phenotypes.
AB - Polytomous phenotypes arise when a disease has multiple subtypes or when two dichotomous phenotypes are analyzed simultaneously. Few software programs offer the option to analyze such phenotypes in family studies, and none implements conditional polytomous logistic regression for within-family analysis robust to population stratification. We introduce Polyunphased, an extension to polytomous phenotypes of the Unphased package, a flexible software tool for genetic association analysis in nuclear families. Like Unphased, Polyunphased is written in C++ and runs from the command line or from a Java graphical user interface. Most Unphased options remain available in Polyunphased, including those handling missing parental genotypes while preserving robustness to population stratification, and the modelling options. Simulation studies confirmed the expected statistical behaviour of the maximum likelihood estimates of the association parameters of the conditional logistic regression model when the corresponding association parameters in the parental term of the likelihood function are set to 0, but revealed convergence problems when estimating these parental association parameters separately. The former approach is thus recommended with polytomous phenotypes.
KW - conditional likelihood
KW - nuclear families
KW - polytomous logistic model
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U2 - 10.1515/sagmb-2016-0035
DO - 10.1515/sagmb-2016-0035
M3 - Article
C2 - 28186960
AN - SCOPUS:85016058487
SN - 1544-6115
VL - 16
SP - 75
EP - 81
JO - Statistical applications in genetics and molecular biology
JF - Statistical applications in genetics and molecular biology
IS - 1
ER -