Testing Hardy-Weinberg equilibrium using mother-child case-control samples.
Genetic association studies of obstetric complications may genotype case and control mothers, or their respective newborns, or both case-control mothers and their children. The relatively high prevalence of many obstetric complications and the availability of both maternal and offspring's genotype data have provided motivation to study new methods for testing for deviations from Hardy-Weinberg equilibrium (HWE). We propose four novel test statistics, each of which uses a different type of data as follows: (1) a test using maternal case-control genotype data, (2) a test using offspring genotype data, (3) a combination of the first and second tests, and (4) a test based on the joint classification of case-control maternal-child genotype data. The selection of case and control mothers (and thus their children) is accounted for by weighting both maternal and child contributions to the test statistics with sampling probabilities. Our tests thus do not require that the phenotype be rare as is the case for HWE tests using only controls, and are particularly suitable for genetic association studies of relatively common complications such as premature birth. The third and fourth tests described above utilize both maternal and child genotype data and appropriately account for the correlation between maternal and child genotypes. On the basis of extensive simulation studies to compare the type-I error and power for proposed tests, we recommend the third combined test statistic for routine use in the analysis of case-control studies of mother-child pairs.
Chen
Jinbo
J
Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. jinboche@mail.med.upenn.edu
Zheng
Haitao
H
Wilson
Melissa L
ML
Kraft
Peter
P
D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy