Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11694-9. Epub 2007 Jul 3.

Probing genetic overlap among complex human phenotypes.

Author information

  • 1Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics and Joint Centers for Systems Biology, Columbia University, New York, NY 10032, USA. ar345@columbia.edu

Abstract

Geneticists and epidemiologists often observe that certain hereditary disorders cooccur in individual patients significantly more (or significantly less) frequently than expected, suggesting there is a genetic variation that predisposes its bearer to multiple disorders, or that protects against some disorders while predisposing to others. We suggest that, by using a large number of phenotypic observations about multiple disorders and an appropriate statistical model, we can infer genetic overlaps between phenotypes. Our proof-of-concept analysis of 1.5 million patient records and 161 disorders indicates that disease phenotypes form a highly connected network of strong pairwise correlations. Our modeling approach, under appropriate assumptions, allows us to estimate from these correlations the size of putative genetic overlaps. For example, we suggest that autism, bipolar disorder, and schizophrenia share significant genetic overlaps. Our disease network hypothesis can be immediately exploited in the design of genetic mapping approaches that involve joint linkage or association analyses of multiple seemingly disparate phenotypes.

PMID:
17609372
[PubMed - indexed for MEDLINE]
PMCID:
PMC1906727
Free PMC Article

Images from this publication.See all images (3)Free text

Fig. 1.
Fig. 2.
Fig. 3.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk