title: Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood.
abstract: CONCLUSIONS
  Genetic correlations are the genome-wide aggregate effects of causal variants affecting multiple traits. Traditionally, genetic correlations between complex traits are estimated from pedigree studies, but such estimates can be confounded by shared environmental factors. Moreover, for diseases, low prevalence rates imply that even if the true genetic correlation between disorders was high, co-aggregation of disorders in families might not occur or could not be distinguished from chance. We have developed and implemented statistical methods based on linear mixed models to obtain unbiased estimates of the genetic correlation between pairs of quantitative traits or pairs of binary traits of complex diseases using population-based case-control studies with genome-wide single-nucleotide polymorphism data. The method is validated in a simulation study and applied to estimate genetic correlation between various diseases from Wellcome Trust Case Control Consortium data in a series of bivariate analyses. We estimate a significant positive genetic correlation between risk of Type 2 diabetes and hypertension of ~0.31 (SE 0.14, P = 0.024).
  
  
  BACKGROUND
  Our methods, appropriate for both quantitative and binary traits, are implemented in the freely available software GCTA (http://www.complextraitgenomics.com/software/gcta/reml_bivar.html).
  
  
  BACKGROUND
  hong.lee@uq.edu.au
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, Australia. hong.lee@uq.edu.au
authors: S H
authors: SH
authors: Lee
authors: J
authors: J
authors: Yang
authors: M E
authors: ME
authors: Goddard
authors: P M
authors: PM
authors: Visscher
authors: N R
authors: NR
authors: Wray
mesh_terms: D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000235:genetics; D016013:Likelihood Functions; D016014:Linear Models; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012984:Software