Format

Send to

Choose Destination
Am J Hum Genet. 2011 Nov 11;89(5):607-18. doi: 10.1016/j.ajhg.2011.10.004.

Abundant pleiotropy in human complex diseases and traits.

Author information

1
Centre for Population Health Sciences, The University of Edinburgh, Edinburgh EH8 9AG, UK.

Abstract

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 pleiotropic 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.

Comment in

PMID:
22077970
PMCID:
PMC3213397
DOI:
10.1016/j.ajhg.2011.10.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center