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Robust partial likelihood approach for detecting imprinting and maternal effects using case-control families. (English) Zbl 1454.62423

Summary: Genomic imprinting and maternal effects are two epigenetic factors that have been increasingly explored for their roles in the etiology of complex diseases. This is part of a concerted effort to find the “missing heritability”. Accordingly, statistical methods have been proposed to detect imprinting and maternal effects simultaneously based on either a case-parent triads design or a case-mother/control-mother pairs design. However, existing methods are full-likelihood based and have to make strong assumptions concerning mating type probabilities (nuisance parameters) to avoid overparametrization. In this paper we propose to augment the two popular study designs by combining them and including control-parent triads, so that our sample may contain a mixture of case-parent/control-parent triads and case-mother/control-mother pairs. By matching the case families with control families of the same structure and stratifying according to the familial genotypes, we are able to derive a partial likelihood that is free of the nuisance parameters. This renders unnecessary any unrealistic assumptions and leads to a robust procedure without sacrificing power. Our simulation study demonstrates that our partial likelihood method has correct type I error rate, little bias and reasonable power under a variety of settings.

MSC:

62P10 Applications of statistics to biology and medical sciences; meta analysis
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References:

[1] Ainsworth, H. F., Unwin, J., Jamison, D. L. and Cordell, H. J. (2011). Investigation of maternal effects, maternal-fetal interactions and parent-of-origin effects (imprinting), using mothers and their offspring. Genet. Epidemiol. 35 19-45.
[2] Cox, D. R. (1975). Partial likelihood. Biometrika 62 269-276. · Zbl 0312.62002
[3] Falls, J. G., Pulford, D. J., Wylie, A. A. and Jirtle, R. L. (1999). Genomic imprinting: Implications for human disease. Am. J. Pathol. 154 635-647.
[4] Giannoukakis, N., Deal, C., Paquette, J., Goodyer, C. G. and Polychronakos, C. (1993). Parental genomic imprinting of the human IGF2 gene. Nat. Genet. 4 98-101.
[5] Gregg, C., Zhang, J., Weissbourd, B., Luo, S., Schroth, G. P., Haig, D. and Dulac, C. (2010). High-resolution analysis of parent-of-origin allelic expression in the mouse brain. Science 329 643-648.
[6] Hager, R., Cheverud, J. M. and Wolf, J. B. (2008). Maternal effects as the cause of parent-of-origin effects that mimic genomic imprinting. Genetics 178 1755-1762.
[7] Haig, D. (1993). Genetic conflicts in human pregnancy. Q. Rev. Biol. 68 495-532.
[8] Haig, D. (2004). Evolutionary conflicts in pregnancy and calcium metabolism-A review. Placenta 25 S10-S15.
[9] Jensen, L. E., Etheredge, A. J., Brown, K. S., Mitchell, L. E. and Whitehead, A. S. (2006). Maternal genotype for the monocyte chemoattractant protein 1 A(-2518)G promotor polymorphism is associated with the risk of spina bifida in offspring. Am. J. Med. Genet. 140A 1114-1118.
[10] Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., Cho, J. H., Guttmacher, A. E., Kong, A., Kruglyak, L., Mardis, E., Rotimi, C. N., Slatkin, M., Valle, D., Whittemore, A. S., Boehnke, M., Clark, A. G., Eichler, E. E., Gibson, G., Haines, J. L., Mackay, T. F. C., McCarroll, S. A. and Visscher, P. M. (2009). Finding the missing heritability of complex diseases. Nature 461 747-753.
[11] Morison, I. M., Paton, C. J. and Cleverley, S. D. (2001). The imprinted gene and parent-of-origin effect database. Nucleic Acids Res. 29 275-276.
[12] Palmer, C. G. S., Hsieh, H.-J., Reed, E. F., Lonnqvist, J., Peltonen, L., Woodward, J. A. and Sinsheimer, J. S. (2006). HLA-B maternal-fetal genotype matching increases risk of schizophrenia. Am. J. Hum. Genet. 79 710-715.
[13] Shi, M., Umbach, D. M., Vermeulen, S. H. and Weinberg, C. R. (2008). Making the most of case-mother/control-mother studies. Am. J. Epidemiol. 168 541-547.
[14] Sinsheimer, J. S., Palmer, C. G. S. and Woodward, J. A. (2003). Detecting genotype combinations that increase risk for disease: The maternal-fetal genotype incomparibility test. Genet. Epidemiol. 24 1-13.
[15] Vermeulen, S. H., Shi, M., Weinberg, C. R. and Umbach, D. M. (2009). A hybrid design: Case-parent triads supplemented by control-mother dyads. Genet. Epidemiol. 33 136-144.
[16] Wang, X., Sun, Q., McGrath, S. D., Mardis, E. R., Soloway, P. D. and Clark, A. G. (2008). Transcriptome-wide identification of novel imprinted genes in neonatal mouse brain. PLoS ONE 3 e3839.
[17] Weinberg, C. R. (1999). Methods for detection of parent-of-origin effects in genetic studies of case-parents triads. Am. J. Hum. Genet. 65 229-235.
[18] Weinberg, C. R. and Umbach, D. M. (2005). A hybrid design for studying genetic influences on risk of diseases with onset early in life. Am. J. Hum. Genet. 77 627-636.
[19] Weinberg, C. R., Wilcox, A. J. and Lie, R. T. (1998). 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. Am. J. Hum. Genet. 62 969-978.
[20] Weir, B. S. (1996). Genetic Data Analysis II . Sinauer, Sunderland, MA.
[21] Yang, J. and Lin, S. (2009). Detection of imprinting and heterogeneous maternal ef- fects on high blood pressure using framingham heart study data. BMC Proceedings 3 S125.
[22] Zhou, J.-Y., Hu, Y.-Q., Lin, S. and Fung, W. K. (2009). Detection of parent-of-origin effects based on complete and incomplete nuclear families with multiple affected children. Hum. Hered. 67 1-12.
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