Score Statistics for Mapping Quantitative Trait Loci

We propose a method to detect the existence of quantitative trait loci (QTL) in a backcross population using a score test. Since the score test only uses the MLEs of parameters under the null hypothesis, it is computationally simpler than the likelihood ratio test (LRT). Moreover, because the location parameter of the QTL is unidentifiable under the null hypothesis, the distribution of the maximum of the LRT statistics, typically the statistic of choice for testing H0: no QTL, does not have the standard chi-square distribution asymptotically under the null hypothesis. From the simple structure of the score test statistics, the asymptotic null distribution can be derived for the maximum of the square of score test statistics. Numerical methods are proposed to compute the asymptotic null distribution and the critical thresholds can be obtained accordingly. We show that the maximum of the LR test statistics and the maximum of the square of score statistics are asymptotically equivalent. Therefore, the critical threshold for the score test can be used for the LR test also. A simple backcross design is used to demonstrate the application of the score test to QTL mapping.

[1]  Albert D. Shieh,et al.  Statistical Applications in Genetics and Molecular Biology , 2010 .

[2]  M. Kupperman Linear Statistical Inference and Its Applications 2nd Edition (C. Radhakrishna Rao) , 1975 .

[3]  Z. Zeng Precision mapping of quantitative trait loci. , 1994, Genetics.

[4]  Rebecca W. Doerge,et al.  Statistical issues in the search for genes affecting quantitative traits in experimental populations , 1997 .

[5]  A. G. Abbott,et al.  Genetic mapping of quantitative trait loci. , 2008 .

[6]  Quantitative genetics of yield breeding for Populus short rotation culture. I. Dynamics of genetic control and selection model of yield traits , 1992 .

[7]  J. V. Ooijen,et al.  Accuracy of mapping quantitative trait loci in autogamous species , 1992, Theoretical and Applied Genetics.

[8]  D. Neale,et al.  Multiple marker mapping of quantitative trait loci in an outbred pedigree of loblolly pine , 1997, Theoretical and Applied Genetics.

[9]  M. Soller,et al.  Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map. , 1993, Genetics.

[10]  R. Jansen Quantitative trait loci in inbred lines , 2004 .

[11]  J. Witte,et al.  Genetic dissection of complex traits , 1996, Nature Genetics.

[12]  B. Mangin,et al.  Approximate thresholds of interval mapping tests for QTL detection. , 1994, Genetics.

[13]  R. Doerge,et al.  Significance thresholds for QTL interval mapping tests , 1996, Heredity.

[14]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[15]  K. Davies,et al.  Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Rongling Wu,et al.  Statistical Genetics of Quantitative Traits: Linkage, Maps and QTL , 2007 .

[17]  Rongling Wu,et al.  Molecular linkage maps of the Populus genome. , 2002, Genome.

[18]  D. Rubin,et al.  Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper , 1977 .

[19]  K. Sax,et al.  The Association of Size Differences with Seed-Coat Pattern and Pigmentation in PHASEOLUS VULGARIS. , 1923, Genetics.

[20]  Rongling Wu,et al.  A general statistical framework for mapping quantitative trait loci in nonmodel systems: issue for characterizing linkage phases. , 2003, Genetics.

[21]  M. Kendall Theoretical Statistics , 1956, Nature.

[22]  R. Davies Hypothesis testing when a nuisance parameter is present only under the alternative , 1977 .

[23]  R. Doerge,et al.  Permutation tests for multiple loci affecting a quantitative character. , 1996, Genetics.

[24]  D Siegmund,et al.  Statistical methods for mapping quantitative trait loci from a dense set of markers. , 1999, Genetics.

[25]  J. Huang,et al.  A score-statistic approach for the mapping of quantitative-trait loci with sibships of arbitrary size. , 2002, American journal of human genetics.

[26]  Mapping quantitative trait loci using four-way crosses , 2008 .

[27]  L. Andersson,et al.  Genetic mapping of quantitative trait loci for growth and fatness in pigs. , 1994, Science.

[28]  N. Barton,et al.  Multifactorial genetics: Understanding quantitative genetic variation , 2002, Nature Reviews Genetics.

[29]  R. Doerge Multifactorial genetics: Mapping and analysis of quantitative trait loci in experimental populations , 2002, Nature Reviews Genetics.

[30]  T. Mackay The genetic architecture of quantitative traits. , 2001, Annual review of genetics.

[31]  E. Lander,et al.  Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. , 1989, Genetics.

[32]  Roger L. Berger,et al.  Likelihood ratio tests and intersection-union tests , 1997 .

[33]  Fei Zou,et al.  An Efficient Resampling Method for Assessing Genome-Wide Statistical Significance in Mapping Quantitative Trait Loci , 2004, Genetics.

[34]  R. Jansen,et al.  University of Groningen High Resolution of Quantitative Traits Into Multiple Loci via Interval Mapping , 2022 .

[35]  D. Schaid,et al.  Score tests for association between traits and haplotypes when linkage phase is ambiguous. , 2002, American journal of human genetics.

[36]  N E Morton,et al.  Error filtration, interference, and the human linkage map. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[37]  H. Piepho A quick method for computing approximate thresholds for quantitative trait loci detection. , 2001, Genetics.

[38]  B. Mangin,et al.  Comparing power of different methods for QTL detection. , 1995, Biometrics.

[39]  I. Hoeschele,et al.  Mapping Quantitative Trait Loci in Outbred Pedigrees , 2004 .

[40]  B. Yandell,et al.  Statistical issues in the analysis of quantitative traits in combined crosses. , 2001, Genetics.