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On the Meta-Analysis of Genome-Wide Association Studies: A Robust and Efficient Approach to Combine Population and Family-Based Studies

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Bertram,  L.
Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Lange,  C.
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Won, S., Lu, Q., Bertram, L., Tanzi, R. E., & Lange, C. (2012). On the Meta-Analysis of Genome-Wide Association Studies: A Robust and Efficient Approach to Combine Population and Family-Based Studies. Human Heredity, 73(1), 35-46. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22261799 http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=000331219&Ausgabe=256765&ProduktNr=224250&filename=000331219.pdf.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-7763-9
Abstract
For the meta-analysis of genome-wide association studies, we propose a new method to adjust for the population stratification and a linear mixed approach that combines family-based and unrelated samples. The proposed approach achieves similar power levels as a standard meta-analysis which combines the different test statistics or p values across studies. However, by virtue of its design, the proposed approach is robust against population admixture and stratification, and no adjustments for population admixture and stratification, even in unrelated samples, are required. Using simulation studies, we examine the power of the proposed method and compare it to standard approaches in the meta-analysis of genome-wide association studies. The practical features of the approach are illustrated with a meta-analysis of three genome-wide association studies for Alzheimer's disease. We identify three single nucleotide polymorphisms showing significant genome-wide association with affection status. Two single nucleotide polymorphisms are novel and will be verified in other populations in our follow-up study.