The availability of dense panels of common single-nucleotide polymorphisms and sequence variants has facilitated the study of statistical features of the genetic architecture of complex traits and diseases via whole-genome regressions (WGRs). At the onset, traits were analyzed trait by trait, but recently, WGRs have been extended for analysis of several traits jointly. The expectation is that such an approach would offer insight into mechanisms that cause trait associations, such as pleiotropy. We demonstrate that correlation parameters inferred using markers can give a distorted picture of the genetic correlation between traits. In the absence of knowledge of linkage disequilibrium relationships between quantitative or disease trait loci and markers, speculating about genetic correlation and its causes (e.g., pleiotropy) using genomic data is conjectural.KEYWORDS genetic correlation; genomic correlation; genomic heritability; linkage disequilibrium; pleiotropy T HE interindividual differences for a trait or disease risk that can be explained by genetic factors, such as trait heritability (h 2 ), the genetic correlation (r G ), and the coheritability between two traits (r G h 1 h 2 ), are very important parameters in quantitative genetic studies of animals, humans, and plants. These quantities play a role in the study of evolution due to artificial and natural selection, and knowledge thereof is required for statistical prediction of outcomes in animal and plant breeding as well as medicine. Traditionally, these parameters have been estimated using phenotypes and pedigrees, e.g., family and twin data in human genetics. The availability of dense panels of common single-nucleotide polymorphisms (SNPs) and of sequence data more recently has made it possible to assess kinship among distantly related individuals (Morton et al. 1971;Thompson 1975;Ritland 1996;Lynch and Ritland 1999). This development has opened new opportunities for study of the genetic architecture of complex traits and diseases. For instance, Yang et al. (2010) suggested using whole-genome regressions (WGRs) (Meuwissen et al. 2001) to assess the proportion of variance of a trait or disease risk that can be explained by a regression of phenotypes on common SNPs or genomic heritability and a related parameter, the "missing heritability." More recently, WGR models have been extended for the analysis of systems of multiple traits, so the concept of genomic correlation also has entered into the picture (Jia and Jannink 2012; Lee et al. 2012). For instance, Maier et al. (2015) used multivariate WGR models and reported estimates of genetic correlations between psychiatric disorders, and Furlotte and Eskin (2015) presented a methodology that incorporates genetic marker information for the analysis of multiple traits that, according to the authors, "provide fundamental insights into the nature of co-expressed genes." In a similar spirit, Korte et al. (2012) argued that multitrait-marker-enabled regressions can be useful for understanding pleiotropy....