A limited dependent variable model for heritability estimation with non-random ascertained samples

Behav Genet. 2002 Mar;32(2):145-51. doi: 10.1023/a:1015257908396.

Abstract

In a questionnaire study, a random sample of Dutch families was asked whether they suffered from asthma and related symptoms. From these families, a selected sample was invited to come to the hospital for further phenotyping. Families were selected if at least one family member reported a history of asthma and the twins were 18 years of age or older. Not all families that were thus selected volunteered, leaving us with a fraction of the original sample. The aim of this paper is to describe a limited dependent variable model that can be used in such situations in order to obtain estimates that are representative of the population from which the sample was originally drawn. The model is a linear (DeFries-Fulker) regression model corrected for sample selection. This correction is possible when (some of) the characteristics that determine whether subjects volunteer (or not) are known for all subjects, including those that did not volunteer. The questionnaire study is of interest by itself but serves mainly to provide a concrete illustration of our method. The present model is used to analyze the data and the results are compared to those obtained with other methods: raw (or direct) likelihood estimation, multiple imputation, and sample weighting. Throughout, Rubin's general theory of inference with missing data serves as an integrating framework.

MeSH terms

  • Adolescent
  • Adult
  • Asthma / genetics*
  • Bias
  • Child
  • Diseases in Twins*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing*
  • Humans
  • Likelihood Functions
  • Male
  • Models, Genetic*
  • Netherlands
  • Phenotype
  • Risk