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

Frontiers in Genetics

Liubov Arbeeva¹  Ilya Zhbannikov¹  Svetlana Ukraintseva¹  Deqing Wu¹  Anatoliy I Yashin¹  Eric Stallard¹  Irina Kulminskaya¹  Igor Akushevich¹  Konstantin G. Arbeev¹  Mikhail Kovtun¹  Arseniy Yashkin¹  Alexander M Kulminski¹ 

[1] Duke University;

关键词: Linkage Disequilibrium;    population genetic structure;    population stratification;    mortality selection;    lack of replication;    causal SNP;   

DOI  :  10.3389/fgene.2016.00188

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown