title: Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity.
abstract: In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture the age-dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age-dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important gene variations that contribute to human aging and longevity.
authors.affiliation: Department of Clinical Biochemistry and Genetics, KKA, Odense University Hospital, Odense, Denmark. qihua.tan@ouh.fyns-amt.dk
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Bathum
authors.forename: L
authors.initials: L
authors.lastname: Christiansen
authors.forename: G
authors.initials: G
authors.lastname: De Benedictis
authors.forename: J
authors.initials: J
authors.lastname: Dahlgaard
authors.forename: N
authors.initials: N
authors.lastname: Frizner
authors.forename: W
authors.initials: W
authors.lastname: Vach
authors.forename: J W
authors.initials: JW
authors.lastname: Vaupel
authors.forename: A I
authors.initials: AI
authors.lastname: Yashin
authors.forename: K
authors.initials: K
authors.lastname: Christensen
authors.forename: T A
authors.initials: TA
authors.lastname: Kruse
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D003718:Denmark; D005787:Gene Frequency; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008136:Longevity / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014427:Twins / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins