title: Prediction of genetic contributions to complex traits using whole genome sequencing data.
abstract: Although markers identified by genome-wide association studies have individually strong statistical significance, their performance in prediction remains limited. Our goal was to use animal breeding genomic prediction models to predict additive genetic contributions for systolic blood pressure (SBP) using whole genome sequencing data with different validation designs. The additive genetic contributions of SBP were estimated via linear mixed model. Rare variants (MAF<0.05) were collapsed through the k-means method to create a "collapsed single-nucleotide polymorphisms." Prediction of the additive genomic contributions of SBP was conducted using genomic Best Linear Unbiased Predictor (GBLUP) and BayesCπ. Estimates of predictive accuracy were compared using common single-nucleotide polymorphisms (SNPs) versus common and collapsed SNPs, and for prediction within and across families. The additive genetic variance of SBP contributed to 18% of the phenotypic variance (h(2) = 0.18). BayesCπ had slightly better prediction accuracies than GBLUP. In both models, within-family predictions had higher accuracies both in the training and testing set than didacross-family design. Collapsing rare variants via the k-means method and adding to the common SNPs did not improve prediction accuracies. The prediction model, including both pedigree and genomic information, achieved a slightly higher accuracy than using either source of information alone. Prediction of genetic contributions to complex traits is feasible using whole genome sequencing and statistical methods borrowed from animal breeding. The relatedness of individuals between the training and testing set strongly affected the performance of prediction models. Methods for inclusion of rare variants in these models need more development.
authors.affiliation: Department of Dairy Science, University of Wisconsin, 1675 Observatory Drive, Madison, WI 53706, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Statistics, University of Wisconsin, 1220 Medical Sciences Center, 1300 University Ave, Madison, WI 53706, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Leng
authors.affiliation: Department of Dairy Science, University of Wisconsin, 1675 Observatory Drive, Madison, WI 53706, USA.
authors.forename: Kent A
authors.initials: KA
authors.lastname: Weigel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, 1069 WARF Building, 610 North Walnut Street, Madison, WI 53726, USA.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI53726, USA.
authors.forename: Corinne D
authors.initials: CD
authors.lastname: Engelman
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, 1069 WARF Building, 610 North Walnut Street, Madison, WI 53726, USA.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Meyers