Synthetic Associations Created by Rare Variants Do Not Explain Most GWAS Results

Naomi R Wray,Peter M Visscher,Shaun M Purcell,Jonathan Flint

doi:10.1371/journal.pbio.1000579

Abstract

Synthetic Associations Created by Rare Variants Do Not Explain Most GWAS Results

Highlights

Complex traits and diseases, such as body-mass index, height, diabetes, heart disease, and psychiatric disorders are undoubtedly caused by multiple genetic and environmental factors, it has been a major challenge to identify specific genes
We found that compared to this average, very common associated single nucleotide polymorphism (SNP) explained a smaller proportion of the total variance than less common variants, implying that the variance explained by the causal variants would have to be very high for such very common alleles to have been detected given the power of typical genome-wide association studies (GWAS) to date
In a GWAS comprising of 3,322 cases and 3,587 controls [12], the International Schizophrenia Consortium (ISC) analysis presented evidence that some common genetic variants contribute to the genetic architecture, demonstrated by the highly significant signal of association of in an independent casecontrol sample based on a profile of the top 50% of associated SNPs from the ISC study

Summary

Introduction

Complex traits and diseases, such as body-mass index, height, diabetes, heart disease, and psychiatric disorders are undoubtedly caused by multiple genetic and environmental factors, it has been a major challenge to identify specific genes. Dickson and colleagues [4,5] recently took a step further, by arguing that rare variants might explain some of the heritability that is currently missing, and that they may be the cause of a proportion of detected associations between complex traits and common SNPs from GWAS. They proposed that some constellations of variants within a narrow frequency and effect size range can account for ‘‘many’’ of the observed associations between complex traits and common SNPs from GWAS This is a strong claim and one that they say has important implications for the ‘‘design of future studies to detect causal variants.’’ It is of great importance to the research.

Dickson et al supported by empirical observation?

Conclusion

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