Incorporating Serotypes into Family Based Association Studies Using the MFG Test

Family based association tests are widely used to detect genetic effects. The focus of this paper is the maternal‐fetal genotype (MFG) incompatibility test, a family based association test which can be used to detect genetic effects that contribute to disease, including alleles in the child that increase disease risk, maternal alleles that increase disease risk in the child, and maternal‐fetal genotype incompatibilities. Consideration of incomplete data resulting from using serotypes could expand the power of the MFG test for detecting genetic effects. Serotypes may be all that are available in certain families, or preferred because of convenience or low cost, and thus a modification of the MFG test will allow optimal use of such data. The modified MFG likelihood can accommodate the incomplete data that result from using serotypes rather than the corresponding codominant genotypes. The modified MFG test was evaluated with serotypes and genotypes from families with members affected with schizophrenia. In addition, simulation studies were performed. Results of the data analyses and simulation studies showed that serotypes can be used to augment genotypes within a sample, to increase power to detect effects when the candidate gene produces serotypes.

[1]  Rhesus Isoimmunization , 2020, Definitions.

[2]  J. Sinsheimer,et al.  A conditional‐on‐exchangeable‐parental‐genotypes likelihood that remains unbiased at the causal locus under multiple‐affected‐sibling ascertainment , 2005, Genetic epidemiology.

[3]  J. Sinsheimer,et al.  An exact maternal‐fetal genotype incompatibility (MFG) test , 2005, Genetic epidemiology.

[4]  Yi-Hau Chen,et al.  New approach to association testing in case‐parent designs under informative parental missingness , 2004, Genetic epidemiology.

[5]  Heather J Cordell,et al.  Properties of case/pseudocontrol analysis for genetic association studies: Effects of recombination, ascertainment, and multiple affected offspring , 2004, Genetic epidemiology.

[6]  Heather J Cordell,et al.  Case/pseudocontrol analysis in genetic association studies: A unified framework for detection of genotype and haplotype associations, gene‐gene and gene‐environment interactions, and parent‐of‐origin effects , 2004, Genetic epidemiology.

[7]  Peter Kraft,et al.  RHD maternal–fetal genotype incompatibility and schizophrenia: extending the MFG test to include multiple siblings and birth order , 2004, European Journal of Human Genetics.

[8]  Janet S Sinsheimer,et al.  Detecting genotype combinations that increase risk for disease: Maternal‐Fetal genotype incompatibility test , 2003, Genetic epidemiology.

[9]  T. Paunio,et al.  RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility. , 2002, American journal of human genetics.

[10]  J D Terwilliger,et al.  Genome-wide scan in a nationwide study sample of schizophrenia families in Finland reveals susceptibility loci on chromosomes 2q and 5q. , 2001, Human molecular genetics.

[11]  J S Sinsheimer,et al.  Chromosome 1 loci in Finnish schizophrenia families. , 2001, Human molecular genetics.

[12]  N. Laird,et al.  The family based association test method: strategies for studying general genotype–phenotype associations , 2001, European Journal of Human Genetics.

[13]  W. Flegel,et al.  RHD gene deletion occurred in the Rhesus box. , 2000, Blood.

[14]  J. Suvisaari,et al.  Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22. , 2000, Human molecular genetics.

[15]  J. Suvisaari,et al.  A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci. , 1999, American journal of human genetics.

[16]  C R Weinberg,et al.  Methods for detection of parent-of-origin effects in genetic studies of case-parents triads. , 1999, American journal of human genetics.

[17]  C R Weinberg,et al.  Allowing for missing parents in genetic studies of case-parent triads. , 1999, American journal of human genetics.

[18]  R. T. Lie,et al.  Distinguishing the effects of maternal and offspring genes through studies of "case-parent triads". , 1998, American journal of epidemiology.

[19]  C R Weinberg,et al.  A log-linear approach to case-parent-triad data: assessing effects of disease genes that act either directly or through maternal effects and that may be subject to parental imprinting. , 1998, American journal of human genetics.

[20]  W J Ewens,et al.  The TDT and other family-based tests for linkage disequilibrium and association. , 1996, American journal of human genetics.

[21]  D J Schaid,et al.  Comparison of statistics for candidate-gene association studies using cases and parents. , 1994, American journal of human genetics.

[22]  D J Schaid,et al.  Genotype relative risks: methods for design and analysis of candidate-gene association studies. , 1993, American journal of human genetics.

[23]  D. Rubin,et al.  Statistical Analysis with Missing Data. , 1989 .

[24]  G. Daniels.  Molecular blood grouping. , 2004, Vox Sanguinis.

[25]  J. Suvisaari,et al.  Genome-wide scan for schizophrenia in the Finnish population : evidence for a locus on chromosome 7 q 22 , 2000 .