Predicting genetic predisposition in humans: the promise of whole-genome markers

Although genome-wide association studies have identified markers that are associated with various human traits and diseases, our ability to predict such phenotypes remains limited. A perhaps overlooked explanation lies in the limitations of the genetic models and statistical techniques commonly used in association studies. We propose that alternative approaches, which are largely borrowed from animal breeding, provide potential for advances. We review selected methods and discuss the challenges and opportunities ahead.

[1]  Robin Thompson,et al.  Estimation of genetic parameters. , 2005 .

[2]  H. Wichmann,et al.  Genes and lifestyle factors in obesity: results from 12 462 subjects from MONICA/KORA , 2010, International Journal of Obesity.

[3]  R. Fisher.  XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance. , 1919, Transactions of the Royal Society of Edinburgh.

[4]  G. Casella,et al.  The Bayesian Lasso , 2008 .

[5]  D Gianola,et al.  Reproducing kernel Hilbert spaces regression: a general framework for genetic evaluation. , 2009, Journal of animal science.

[6]  A. Rao,et al.  Estimation of Genetic Parameters: principles , 2003 .

[7]  Christian Gieger,et al.  Six new loci associated with body mass index highlight a neuronal influence on body weight regulation , 2009, Nature Genetics.

[8]  P. Visscher,et al.  Common SNPs explain a large proportion of heritability for human height , 2011 .

[9]  L. Perlemuter.  [From theory to practice]. , 1997, Soins. Psychiatrie.

[10]  Judy H. Cho,et al.  Finding the missing heritability of complex diseases , 2009, Nature.

[11]  Daniel Gianola,et al.  Theory and Analysis of Threshold Characters , 1982 .

[12]  José Crossa,et al.  Semi-parametric genomic-enabled prediction of genetic values using reproducing kernel Hilbert spaces methods. , 2010, Genetics research.

[13]  Daniel J Schaid,et al.  Genomic Similarity and Kernel Methods I: Advancements by Building on Mathematical and Statistical Foundations , 2010, Human Heredity.

[14]  A. Cecile J.W. Janssens,et al.  Predicting Type 2 Diabetes Based on Polymorphisms From Genome-Wide Association Studies , 2008, Diabetes.

[15]  R. Fernando,et al.  The Impact of Genetic Relationship Information on Genome-Assisted Breeding Values , 2007, Genetics.

[16]  R. Tibshirani.  Regression Shrinkage and Selection via the Lasso , 1996 .

[17]  D. Falconer,et al.  Introduction to Quantitative Genetics. , 1962 .

[18]  Arthur E. Hoerl,et al.  Ridge Regression: Biased Estimation for Nonorthogonal Problems , 2000, Technometrics.

[19]  A. Dominiczak,et al.  Genetics of common polygenic stroke , 2003, Nature Genetics.

[20]  W. G. Hill,et al.  Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits , 2008, PLoS genetics.

[21]  L. Penrose,et al.  THE CORRELATION BETWEEN RELATIVES ON THE SUPPOSITION OF MENDELIAN INHERITANCE , 2022 .

[22]  H. Piepho.  Ridge Regression and Extensions for Genomewide Selection in Maize , 2009 .

[23]  José Crossa,et al.  Prediction of Genetic Values of Quantitative Traits in Plant Breeding Using Pedigree and Molecular Markers , 2010, Genetics.

[24]  Robert Tibshirani,et al.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction, 2nd Edition , 2001, Springer Series in Statistics.

[25]  Peter M Visscher,et al.  Prediction of individual genetic risk to disease from genome-wide association studies. , 2007, Genome research.

[26]  S. Wright,et al.  Systems of Mating. I. the Biometric Relations between Parent and Offspring. , 1921, Genetics.

[27]  C. R. Henderson,et al.  Best linear unbiased estimation and prediction under a selection model. , 1975, Biometrics.

[28]  George E. P. Box,et al.  Empirical Model‐Building and Response Surfaces , 1988 .

[29]  Robert Tibshirani,et al.  Survival analysis with high-dimensional covariates , 2010, Statistical methods in medical research.

[30]  D Gianola,et al.  Predictive ability of direct genomic values for lifetime net merit of Holstein sires using selected subsets of single nucleotide polymorphism markers. , 2009, Journal of dairy science.

[31]  M. Goddard.  Genomic selection: prediction of accuracy and maximisation of long term response , 2009, Genetica.

[32]  Kent A Weigel,et al.  Nonparametric Methods for Incorporating Genomic Information Into Genetic Evaluations: An Application to Mortality in Broilers , 2008, Genetics.

[33]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[34]  B. Maher.  Personal genomes: The case of the missing heritability , 2008, Nature.

[35]  M. Goddard,et al.  Invited review: Genomic selection in dairy cattle: progress and challenges. , 2009, Journal of dairy science.

[36]  M. Goddard,et al.  Mapping genes for complex traits in domestic animals and their use in breeding programmes , 2009, Nature Reviews Genetics.

[37]  T. H. E. Meuwissen,et al.  Marker based estimates of between and within population kinships for the conservation of genetic diversity , 2001 .

[38]  H. Tiwari,et al.  A new estimate of family disease history providing improved prediction of disease risks , 2009, Statistics in medicine.

[39]  鮫島 浩,et al.  Population-based study からみた神経予後不良因子の検討 , 2009 .

[40]  D. Gianola,et al.  Reproducing Kernel Hilbert Spaces Regression Methods for Genomic Assisted Prediction of Quantitative Traits , 2008, Genetics.

[41]  K. Weigel,et al.  Radial basis function regression methods for predicting quantitative traits using SNP markers. , 2010, Genetics research.

[42]  Andrés Legarra,et al.  Performance of Genomic Selection in Mice , 2008, Genetics.

[43]  Joseph T. Glessner,et al.  The Role of Obesity‐associated Loci Identified in Genome‐wide Association Studies in the Determination of Pediatric BMI , 2009, Obesity.

[44]  Jean-Luc Jannink,et al.  Genomic selection in plant breeding: from theory to practice. , 2010, Briefings in functional genomics.

[45]  M. Goddard,et al.  Prediction of total genetic value using genome-wide dense marker maps. , 2001, Genetics.

[46]  G. Box,et al.  Empirical Model-Building and Response Surfaces. , 1990 .

[47]  G. Wahba,et al.  A Correspondence Between Bayesian Estimation on Stochastic Processes and Smoothing by Splines , 1970 .

[48]  O. Kempthorne.  The correlation between relatives on the supposition of mendelian inheritance , 1968 .

[49]  G. Wahba.  Spline models for observational data , 1990 .

[50]  W. G. Hill,et al.  Understanding and using quantitative genetic variation , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[51]  A. Templeton.  Systems of Mating , 2006, Population Genetics and Microevolutionary Theory.

[52]  R. Fernando,et al.  Genomic-Assisted Prediction of Genetic Value With Semiparametric Procedures , 2006, Genetics.

[53]  Tanaka.  The role of , 2000, Journal of insect physiology.

[54]  Shosuke Ito,et al.  Predicting Phenotype from Genotype: Normal Pigmentation * , 2010, Journal of forensic sciences.

[55]  Nello Cristianini,et al.  Kernel Methods for Pattern Analysis , 2003, ICTAI.

[56]  M. Goddard,et al.  Technical note: prediction of breeding values using marker-derived relationship matrices. , 2008, Journal of animal science.

[57]  K. S. Banerjee,et al.  A Comment on Ridge Regression. Biased Estimation for Non-Orthogonal Problems , 1971 .

[58]  H. Zou,et al.  Regularization and variable selection via the elastic net , 2005 .

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

[60]  Jean-Luc Jannink,et al.  Factors Affecting Accuracy From Genomic Selection in Populations Derived From Multiple Inbred Lines: A Barley Case Study , 2009, Genetics.

[61]  P. VanRaden,et al.  Invited review: reliability of genomic predictions for North American Holstein bulls. , 2009, Journal of dairy science.

[62]  Francis S. Collins,et al.  Genomic medicine--a primer. , 2002, The New England journal of medicine.

[63]  M. Lynch,et al.  Estimation of pairwise relatedness with molecular markers. , 1999, Genetics.

[64]  José Crossa,et al.  Predicting Quantitative Traits With Regression Models for Dense Molecular Markers and Pedigree , 2009, Genetics.

[65]  B. Maher,et al.  The case of the missing heritability , 2008 .

[66]  O. Kempthorne,et al.  The correlation between relatives in a random mating population , 1954, Proceedings of the Royal Society of London. Series B - Biological Sciences.

[67]  Manuel A. R. Ferreira,et al.  Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings , 2006, PLoS genetics.

[68]  Sudha Seshadri,et al.  Genome-wide analysis of genetic loci associated with Alzheimer disease. , 2010, JAMA.

[69]  C. Cockerham,et al.  An Extension of the Concept of Partitioning Hereditary Variance for Analysis of Covariances among Relatives When Epistasis Is Present. , 1954, Genetics.