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Abundant Pleiotropy in Human Complex Diseases and Traits

Summary: ARTICLE
Abundant Pleiotropy in Human Complex
Diseases and Traits
Shanya Sivakumaran,1,6 Felix Agakov,1,2,6 Evropi Theodoratou,1,6 James G. Prendergast,3 Lina Zgaga,1,4
Teri Manolio,5 Igor Rudan,1 Paul McKeigue,1 James F. Wilson,1 and Harry Campbell1,*
We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex
diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleio-
tropic status was associated with gene location (p 0.024; pleiotropic SNPs more often exonic [14.5% versus 4.9% for nonpleiotropic,
trait-associated SNPs] and less often intergenic [15.8% versus 23.6%]), ``predicted transcript consequence'' (p 0.001; pleiotropic SNPs
more often predicted to be structurally deleterious [5% versus 0.4%] but not more often in regulatory sequences), and certain disease
classes. We develop a method to calculate the likelihood that pleiotropic links between traits occurred more often than expected and
demonstrate that this approach can identify etiological links that are already known (such as between fetal hemoglobin and malaria
risk) and those that are not yet established (e.g., between plasma campesterol levels and gallstones risk; and between immunoglobulin
A and juvenile idiopathic arthritis). Examples of pleiotropy will accumulate over time, but it is already clear that pleiotropy is a common
property of genes and SNPs associated with disease traits, and this will have implications for identification of molecular targets for drug
development, future genetic risk-profiling, and classification of diseases.
Pleiotropy occurs when one gene has an effect on multiple
phenotypes. The molecular mechanisms of pleiotropy can
be dichotomized into multiple molecular functions of a


Source: Agakov, Felix - Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh


Collections: Computer Technologies and Information Sciences