Exploiting pleiotropy to map genes for oligogenic phenotypes using extended pedigree data

Genetic Epidemiology
Anthony G ComuzzieJ Blangero

Abstract

We investigated the utility of two approaches for exploiting pleiotropy to search for genes influencing related traits. To do this we first assessed the genetic correlations among a set of five closely related quantitative traits (Q1, Q2, Q3, Q4, Q5). We then used the genetic correlations among these five traits both to remove the common genetic effects of the four remaining traits, thereby identifying the unique genetic contribution to each trait, and to extract a synthetic phenotype which exploits the shared genetic information (pleiotropy) among these five traits. After obtaining these conditional traits, we then searched for evidence of quantitative trait loci (QTLs) (using variance component linkage) influencing the unique residual genetic component for each trait as well as those influencing the expression of the synthetic traits. From this work, we conclude that the removal of the common genetic effects of other traits in a group may be of greater utility when the majority of the pleiotropy initially detected between traits is attributable to the shared additive effects of polygenes, rather than to those of major loci. By contrast, decomposition of the genetic covariance matrix to its principal components is a greater ut...Continue Reading

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References

Jan 1, 1991·Genetic Epidemiology·J Blangero, L W Konigsberg
Oct 1, 1982·Annals of Human Genetics·J L Hopper, J D Mathews
Feb 1, 1996·Arteriosclerosis, Thrombosis, and Vascular Biology·A G ComuzzieJ W MacCluer
Jan 1, 1995·Genetic Epidemiology·M C MahaneyA G Comuzzie
May 1, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·A G ComuzzieJ W MacCluer

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Citations

May 10, 2008·BMC Proceedings·Anthony L HinrichsBrian K Suarez
Jul 14, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·R D Blank
Sep 27, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·D Reese McKayPeter T Fox
Nov 26, 2003·Genetic Epidemiology·Yohan BosséLouis Pérusse
Sep 6, 2005·Annals of Human Genetics·L E BaumanK Lange
Oct 16, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·K L EdwardsM A Austin
Apr 30, 2020·Statistics in Medicine·Adèle H Ribeiro, Júlia Maria Pavan Soler

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