Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper Interpretation of Research Findings in GWAS of Populations with Different Genetic Structures.

Abstract

This paper shows that the effects of causal SNPs on lifespan, estimated through GWAS, may be confounded and the genetic structure of the study population may be responsible for this effect. Simulation experiments show that levels of linkage disequilibrium (LD) and other parameters of the population structure describing connections between two causal SNPs may substantially influence separate estimates of the effect of the causal SNPs on lifespan. This study suggests that differences in LD levels between two causal SNP loci within two study populations may contribute to the failure to replicate previous GWAS findings. The results of this paper also show that successful replication of the results of genetic association studies does not necessarily guarantee proper interpretation of the effect of a causal SNP on lifespan.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.3389/fgene.2016.00188

Publication Info

Yashin, Anatoliy I, Ilya Zhbannikov, Liubov Arbeeva, Konstantin G Arbeev, Deqing Wu, Igor Akushevich, Arseniy Yashkin, Mikhail Kovtun, et al. (2016). Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper Interpretation of Research Findings in GWAS of Populations with Different Genetic Structures. Front Genet, 7. p. 188. 10.3389/fgene.2016.00188 Retrieved from https://hdl.handle.net/10161/14751.

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Scholars@Duke

Yashin

Anatoli I. Yashin

Research Professor in the Social Science Research Institute
Zhbannikov

Ilya Zhbannikov

Biostatistician III
Arbeev

Konstantin Arbeev

Associate Research Professor in the Social Science Research Institute

Konstantin G. Arbeev received the M.S. degree in Applied Mathematics from Moscow State University (branch in Ulyanovsk, Russia) in 1995 and the Ph.D. degree in Mathematics and Physics (specialization in Theoretical Foundations of Mathematical Modeling, Numerical Methods and Programming) from Ulyanovsk State University (Russia) in 1999. He was a post-doctoral fellow in Max Planck Institute for Demographic Research in Rostock (Germany) before moving to Duke University in 2004 to work as a Research Scientist and a Senior Research Scientist in the Department of Sociology and the Social Science Research Institute (SSRI).  He is currently an Associate Research Professor in SSRI. Dr. Arbeev's major research interests are related to three interconnected fields of biodemography, biostatistics and genetic epidemiology as pertains to research on aging. The focus of his research is on discovering genetic and non-genetic factors that can affect the process of aging and determine longevity and healthy lifespan. He is interested in both methodological advances in this research area as well as their practical applications to analyses of large-scale longitudinal studies with phenotypic, genetic and, recently, genomic information. Dr. Arbeev authored and co-authored more than 150 peer-reviewed publications in these areas.

Wu

Dequing Wu

Research Scientist, Senior

Igor Akushevich

Research Professor in the Social Science Research Institute

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