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Mapping complex disease loci in whole-genome association studies

Abstract

Identification of the genetic polymorphisms that contribute to susceptibility for common diseases such as type 2 diabetes and schizophrenia will aid in the development of diagnostics and therapeutics. Previous studies have focused on the technique of genetic linkage, but new technologies and experimental resources make whole-genome association studies more feasible. Association studies of this type have good prospects for dissecting the genetics of common disease, but they currently face a number of challenges, including problems with multiple testing and study design, definition of intermediate phenotypes and interaction between polymorphisms.

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Figure 1: Direct versus indirect association analysis.
Figure 2: Pathway of physical interactions.

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Acknowledgements

This work was supported by grants from the National Heart, Lung and Blood Institute, the National Institute of Environmental Health Sciences and the National Institute of Mental Health. L.K. is a James S. McDonnell Centennial Fellow. Thanks to D. Altshuler for helpful input, to G. Jarvik, P. Heagerty and P. Scheet for discussions on epistatic risk models, and to T. Banghale, D. Crawford, B. Livingston, R. Mackelprang and M. Rieder for comments on the manuscript.

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L.K. consults for and holds equity in companies involved in SNP technologies and association studies. C.S.C. and D.A.N. consult for companies working on SNP diagnostics and genotyping technologies

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Carlson, C., Eberle, M., Kruglyak, L. et al. Mapping complex disease loci in whole-genome association studies. Nature 429, 446–452 (2004). https://doi.org/10.1038/nature02623

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