IngentaConnect Estimation of Individual Genetic Effects from Binary Observations...

Authors: Houwing-Duistermaat, Jeanine J.¹; Houwelingen, Hans C.²; Winter, J. Peter³

Source: Biometrics, Volume 56, Number 3, September 2000 , pp. 808-814(7)

Abstract:

Summary.

This paper considers methods for estimating the relationship between a binary response Y and the genetic effects responsible for a second binary trait Z. The responses Y are observed only for target individuals, and the responses Z are observed only for the relatives of these targets. The analysis consists of two parts. The first part concerns the analysis of the family data Z and the second part estimates the relation between the genetic effects and Y. For the family data, a generalized linear mixed model with a logit link and Gaussian genetic (random) effects is used. Estimates of the variances of the genetic effects are obtained by using a pseudo-profile log-likelihood method. Estimation of the log likelihood involves averaging over n-dimensional normal distributions, which is done by importance sampling. The methods used in the second part are straightforward. The methods are applied to a data set containing chronic lung disease (CLDN) responses of newborns and asthma (AS), allergy (AL), chronic bronchitis (CB) and eczema (EC) responses observed for the relatives of these newborns. The clinical question is whether genetic effects of AS, AL, CB, and EC have an effect on the risk for CLDN. It can be concluded that for AS, AL, CB, and EC, the influence of genetic effects is significant. However, these genetic predispositions have no significant effect on CLDN.

Keywords: Correlated binary observations; Family history; Genetic effects; Importance sampling; Logistic models with Gaussian random effects; Profile log likelihood

Document Type: Research article

DOI: 10.1111/j.0006-341X.2000.00808.x

Affiliations: 1: Institute of Epidemiology and Biostatistics, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands 2: Department of Medical Statistics, Leiden University, Leiden, The Netherlands 3: Department of Neonatology, Utrecht Medical Center, Wilhelmina Children's Hospital, Utrecht, The Netherlands

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Estimation of Individual Genetic Effects from Binary Observations on Relatives Applied to a Family History of Respiratory Illnesses and Chronic Lung Disease of Newborns