Cautions of Using Allele-Based Tests Under Heterosis
DOI:
https://doi.org/10.6000/1929-6029.2013.02.01.06Keywords:
Chi-square test, dynamic systems theory, genotype, haplotype, statistical powerAbstract
:In genetic studies, heterotic effects are commonly assessed as dominant, additive, or recessive effects for a given genetic marker. However, the distorting effect of heterosis on statistical tests is non-trivial. An inheritance model needs to be carefully chosen to achieve highest testing power. We assess this through simulations via allele- and genotype-based tests. Chi-square test statistics for different inheritance models are formulated as a function of relative risks and allele frequencies. The results indicate that testing power from the commonly used allele-based tests can be substantially diminished by heterosis. Assessing the existence of heterosis is thus recommended to avoid false negative findings.
References
Comings DE, MacMurray JP. Molecular heterosis: a review. Mol Genet Metab 2000; 71: 19-31. http://dx.doi.org/10.1006/mgme.2000.3015 DOI: https://doi.org/10.1006/mgme.2000.3015
Thelen E, Smith LB. Dynamic Systems Theories. In: Damon W, Lerner RM, editors. Handbook of Child Psychology Volume 1, Theoretical Models of Human Development. 6th ed. 2006; pp. 258-312.
Jones DF. Dominance of linked factors as a means of accounting for heterosis. Genetics 1917; 2: 466-79. DOI: https://doi.org/10.1093/genetics/2.5.466
Lipman ZB, Samir D. Heterosis: revisiting the magic. Trends Genet 2007; 23: 60-66. http://dx.doi.org/10.1016/j.tig.2006.12.006 DOI: https://doi.org/10.1016/j.tig.2006.12.006
Crow JF. Mid-century controversies in population genetics. Annu Rev Genet 2008; 42: 1-16. http://dx.doi.org/10.1146/annurev.genet.42.110807.091612 DOI: https://doi.org/10.1146/annurev.genet.42.110807.091612
Chen ZJ. Molecular mechanisms of polyploidy and hybrid vigor. Trends Plant Sci 2010; 15: 57-71. http://dx.doi.org/10.1016/j.tplants.2009.12.003 DOI: https://doi.org/10.1016/j.tplants.2009.12.003
Hochholdinger F, Hoecker N. Towards the molecular basis of heterosis. Trends Plant Sci 2007; 12: 427-32. http://dx.doi.org/10.1016/j.tplants.2007.08.005 DOI: https://doi.org/10.1016/j.tplants.2007.08.005
Penrose LS. Evidence of heterosis in man. In: Pros R Sock Lund B Biol Sci 1955; 144: 203-13. DOI: https://doi.org/10.1098/rspb.1955.0047
Duvick DN. Heterosis: feeding people and protecting natural resources. In: Coors JG, Pander S, editors, The genetics and Exploitation of Heterosis in Crops. American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America 1999; pp. 19-29. DOI: https://doi.org/10.2134/1999.geneticsandexploitation.c3
Duvick DN. Biotechnology in the 1930s: the development of hybrid maize. Nat Rev Genet 2001; 2: 69-74. http://dx.doi.org/10.1038/35047587 DOI: https://doi.org/10.1038/35047587
Marshall DM. Breed differences and genetic parameters for body composition traits in beef cattle. J Amin Sci 1994; 72: 2745-55. DOI: https://doi.org/10.2527/1994.72102745x
Hedrick PW. Population genetics of malaria resistance in humans. Heredity 2011; 107: 283-304. http://dx.doi.org/10.1038/hdy.2011.16 DOI: https://doi.org/10.1038/hdy.2011.16
Comings DE. Molecular heterosis as the explanation for the controversy about the effect of the drd2 gene on dopamine d2 receptor density. Mol Psychiatry 1999; 4: 213-15. http://dx.doi.org/10.1038/sj.mp.4000500 DOI: https://doi.org/10.1038/sj.mp.4000500
Reuter M, Hannig J, Ambling M, et al. The role of the tph1 and tph2 genes for nicotine dependence: a genetic association study in two different age cohorts. Neuropsychobiology 2007; 56: 47-54. http://dx.doi.org/10.1159/000110728 DOI: https://doi.org/10.1159/000110728
Gosso MF, de Geus EJ, Polderman TJ, Boomsma DI, Heutink P, Posthuma D. Catechol o-methyl transferase and dopamine d2 receptor gene polymorphisms: evidence of positive heterosis and gene-gene interaction on working memory functioning. Eur J Hum Genet 2008; 16: 1075-82. http://dx.doi.org/10.1038/ejhg.2008.57 DOI: https://doi.org/10.1038/ejhg.2008.57
Eny KM, Corey PN, El-Sohemy A. Dopamine d2 receptor genotype (c957t) and habitual consumption of sugars in a free-living population of men and women. J Nutrigenet Nutrigenomics 2: 235-42. DOI: https://doi.org/10.1159/000276991
Morahan G, Huang D, Wu M, et al. Association of IL 12b promoter polymorphism with severity of atopic and non-atopic asthma in children. Lancet 2002; 360: 455-59. http://dx.doi.org/10.1016/S0140-6736(02)09676-9 DOI: https://doi.org/10.1016/S0140-6736(02)09676-9
Amos CI. Successful design and conduct of genome-wide association studies. Hum Mol Genet 2007; 16(2): R220-225. http://dx.doi.org/10.1093/hmg/ddm161 DOI: https://doi.org/10.1093/hmg/ddm161
Gail MH, Pee D, Benichou J, Carroll R. Designing studies to estimate the penetrance of an identified autosomal dominant mutation: cohort, case-control, and genotyped-proband designs. Genet Epidemiol 1999; 16: 15-39. http://dx.doi.org/10.1002/(SICI)1098-2272(1999)16:1<15::AID-GEPI3>3.0.CO;2-8 DOI: https://doi.org/10.1002/(SICI)1098-2272(1999)16:1<15::AID-GEPI3>3.0.CO;2-8
Mitra SK. On the limiting power function of the frequency chi-square test. Ann Math Statist 19: 1221-33. DOI: https://doi.org/10.1214/aoms/1177706453
Eyduran E, Ozdemir T, Kazim MK, Keskin S, Cak B. A study of power of chi-square and g statistics in biological sciences. Pak J Biol Sci 2006; 9: 1324-27. http://dx.doi.org/10.3923/pjbs.2006.1324.1327 DOI: https://doi.org/10.3923/pjbs.2006.1324.1327
Minnelli C, Thompson JR, Abrams KR, Thakkinstian A, Attia J. The choice of a genetic model in the meta-analysis of molecular association studies. Int J Epidemiol 2005; 34: 1319-28. http://dx.doi.org/10.1093/ije/dyi169 DOI: https://doi.org/10.1093/ije/dyi169
Arshad SH, Hide DW. Effect of environmental factors on the development of allergic disorders in infancy. J Allergy Clin Immunol 1992; 90: 235-41. http://dx.doi.org/10.1016/0091-6749(92)90077-F DOI: https://doi.org/10.1016/0091-6749(92)90077-F
Howard TD, Whittacker PA, Zaiman AL, Koppelman GH, Xu J, Hanley MT, et al. Identification of association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population. Am J Respirat Cell Mol Biol 2001; 25: 377-84. DOI: https://doi.org/10.1165/ajrcmb.25.3.4483
Kruglyak L, Nickerson DA. Variation is the spice of life. Nat Genet 2001; 27: 234-36. http://dx.doi.org/10.1038/85776 DOI: https://doi.org/10.1038/85776
Clark AG. Inference of haplotypes from PCR-amplified samples of diploid populations. Mol Biol Evol 1990; 7: 111-22.
Xu J. Extracting haplotypes from diploid organisms. Curr Issues Mol Biol 2006; 8: 113-22.
Garner C, Slatkin M. On selecting markers for association studies: patterns of linkage disequilibrium between two and three diallelic loci. Genet Epidemiol 2003; 24: 57-67. http://dx.doi.org/10.1002/gepi.10217 DOI: https://doi.org/10.1002/gepi.10217
Thorleifsson G, Walters GB, Gudbjartsson DF, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009; 41: 18-24. http://dx.doi.org/10.1038/ng.274 DOI: https://doi.org/10.1038/ng.274
Birchler JA, Auger DL, Riddle NC. In search of the molecular basis of heterosis. Plant Cell 2003; 15: 2236-39. http://dx.doi.org/10.1105/tpc.151030 DOI: https://doi.org/10.1105/tpc.151030
Hart SP. Il12b promoter polymorphism and asthma. Lancet 2002; 360: 2085. http://dx.doi.org/10.1016/S0140-6736(02)11980-5 DOI: https://doi.org/10.1016/S0140-6736(02)11980-5
Birchler JA, Auger DL, Riddle NC. Homing in on the asthma gene. Lancet 2002; 360: 422-23. http://dx.doi.org/10.1016/S0140-6736(02)09693-9 DOI: https://doi.org/10.1016/S0140-6736(02)09693-9
Sobacchi C, Vezzoni P, Reid DM, et al. Association between a polymorphism affecting an ap1 binding site in the promoter of the tcirg1 gene and bone mass in women. Calcif Tissue Int 2004; 74: 35-41. http://dx.doi.org/10.1007/s00223-002-0004-2 DOI: https://doi.org/10.1007/s00223-002-0004-2
Lehmann DJ, Cortina-Borja M, Warden DR, et al. Large meta-analysis establishes the ace insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol 2005; 162: 305-17. http://dx.doi.org/10.1093/aje/kwi202 DOI: https://doi.org/10.1093/aje/kwi202
Lee HS. Gender-specific molecular heterosis and association studies: dopamine d2 receptor gene and smoking. Am J Med Genet B Neuropsychiatr Genet 2003; 118B: 55-59. http://dx.doi.org/10.1002/ajmg.b.10036 DOI: https://doi.org/10.1002/ajmg.b.10036
Zheng G, Ng HK. Genetic model selection in two-phase analysis for case control association studies. Biostatistics 2008; 9: 391-99. http://dx.doi.org/10.1093/biostatistics/kxm039 DOI: https://doi.org/10.1093/biostatistics/kxm039
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