Dominance Genetic Variation Contributes Little to the Missing Heritability for Human Complex Traits  Zhihong Zhu, Andrew Bakshi, Anna A.E. Vinkhuyzen, Gibran Hemani, Sang Hong Lee, Ilja M. Nolte, Jana V. van Vliet-Ostaptchouk, Harold Snieder, Tonu Esko, Lili Milani, Reedik Mägi, Andres Metspalu, William G. Hill, Bruce S. Weir, Michael E. Goddard, Peter M. Visscher, Jian Yang  The American Journal of Human Genetics  Volume 96, Issue 3, Pages 377-385 (March 2015) DOI: 10.1016/j.ajhg.2015.01.001 Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 1 Off-Diagonal Elements of the Additive GRM against Those of the Dominance GRM The correlation is 3.40 × 10−4, which is not significantly different from zero (p = 0.11). The American Journal of Human Genetics 2015 96, 377-385DOI: (10.1016/j.ajhg.2015.01.001) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 2 Distribution of the Estimates of hSNP2 and δSNP2 for 79 Traits in the ARIC Cohort To get an unbiased estimate of the mean of hSNP2 or δSNP2 across all the traits, the estimates of hSNP2 and δSNP2 for each trait were not constrained to be positive in the REML analysis. The mean estimates of hSNP2 and δSNP2 are 0.15 and 0.03, respectively. The American Journal of Human Genetics 2015 96, 377-385DOI: (10.1016/j.ajhg.2015.01.001) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 3 Estimates of hSNP2 and δSNP2 in Three Independent Cohorts of ARIC, EGCUT, and LL and in the Combined Dataset of EGCUT and LL for Four Traits Error bar represents the standard error. The American Journal of Human Genetics 2015 96, 377-385DOI: (10.1016/j.ajhg.2015.01.001) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 4 Genome-wide Association Tests for Dominance Effects for Factor VIII and von Willebrand Factor (A and B) Manhattan plots of p values for dominance effects from the model of fitting both additive and dominance effects for factor VIII (FVIII) (A) and von Willebrand factor (vWF) (B). SNPs with genome-wide significant dominance effects are located at the ABO gene locus. (C and D) Genotype-phenotype maps at the top SNP rs505922 for FVIII (C) and the top SNP rs612169 for vWF (D). The normalized phenotypic means in the three genotypic classes are −0.57, 0.12, and 0.30 at the SNP rs505922 for FVIII (C), and −0.57, 0.15, and 0.37 at the SNP rs612169 for vWF (D). Bars represent 2.5% and 97.5% quartiles of the phenotype distribution at each of the three genotypic classes. The American Journal of Human Genetics 2015 96, 377-385DOI: (10.1016/j.ajhg.2015.01.001) Copyright © 2015 The American Society of Human Genetics Terms and Conditions