Incorporating Serotypes into Family Based Association Studies Using the MFG Test

doi:10.1111/j.1469-1809.2005.00243.x

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Wiley InterScience

Annals of Human Genetics

Volume 70 Issue 4, Pages 541 - 553

Published Online: 3 Mar 2006

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Incorporating Serotypes into Family Based Association Studies Using the MFG Test

S. L. Minassian ^1,2,*, C. G. S. Palmer ³ , J. A. Turunen ⁴ T. Paunio ⁴ , J. Lönnqvist ⁵ , L. Peltonen ⁴ , J. A. Woodward ⁶ and J. S. Sinsheimer ^2,7,8,†

¹ Elan Pharmaceuticals, San Diego, California ² Department of Biostatistics, University of California, Los Angeles, California ³ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California ⁴ Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland ⁵ Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland ⁶ Department of Psychology, University of California, Merced, California ⁷ Department of Human Genetics, University of California, Los Angeles, California ⁸ Department of Biomathematics, University of California, Los Angeles, California

^† Corresponding author: Janet Sinsheimer, Ph.D., AV-617 Center for Health Sciences, Dept of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1766, Fax (310) 825-8685. E-mail: janet@mednet.ucla.edu

*Present Affiliation: Elan Pharmaceuticals.

KEYWORDS

gene by environment • gene by gene • maternal-fetal genotype incompatibility • missing data • non-codominant data • rhesus incompatibility • serotypes

ABSTRACT

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.

Received: 25 November 2004
Accepted: 13 September 2005

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1469-1809.2005.00243.x About DOI