GWEHS: A Genome-Wide Effect Sizes and Heritability Screener.

López-Cortegano López-Cortegano,Caballero Caballero

doi:10.3390/genes10080558

Abstract

During the last decade, there has been a huge development of Genome-Wide Association Studies (GWAS), and thousands of loci associated to complex traits have been detected. These efforts have led to the creation of public databases of GWAS results, making a huge source of information available on the genetic background of many diverse traits. Here we present GWEHS (Genome-Wide Effect size and Heritability Screener), an open-source online application to screen loci associated to human complex traits and diseases from the NHGRI-EBI GWAS Catalog. This application provides a way to explore the distribution of effect sizes of loci affecting these traits, as well as their contribution to heritability. Furthermore, it allows for making predictions on the change in the expected mean effect size, as well as in the heritability as new loci are found. The application enables inferences on whether the additive contribution of loci expected to be discovered in the future will be able to explain the estimates of familial heritability for the different traits. We illustrate the use of this tool, compare some of the results obtained with those from a previous meta-analysis, and discuss its uses and limitations.

Highlights

Genome-Wide Association Studies (GWAS) have become the standard tool to find new loci underlying the genetic basis of many complex traits and diseases [1], yet the nature of their genetic architecture, i.e., the number and relative contribution of loci to genetic variation, is mostly unknown [2,3].though thousands of SNPs have been found for many human traits, most of their genetic variance remains unexplained [4,5].It is generally accepted that this missing heritability is mainly due to the additive contribution of hundreds to thousands of loci of small effect size that are not detected by current GWAS because of a lack of statistical power [6,7]
Effect size and Heritability Screener), an open-source online application to screen loci associated to human complex traits and diseases from the NHGRI-EBI GWAS Catalog
We provide a new resource tool that will let researchers mine the GWAS Catalog and explore the genetic background and architecture of a large number of complex traits and diseases, as well as to make rough inferences on their missing heritability

Summary

Introduction

Though thousands of SNPs (single nucleotide polymorphisms) have been found for many human traits, most of their genetic variance remains unexplained (i.e., the missing heritability problem) [4,5]. It is generally accepted that this missing heritability is mainly due to the additive contribution of hundreds to thousands of loci of small effect size that are not detected by current GWAS because of a lack of statistical power [6,7]. It has been suggested that familial estimates of narrow-sense heritability could be overestimated because of environmental and non-additive genetic components of variation [10], as well as different sources of genotype-covariance factors [4,11,12,13]. It is possible that the heritability explained by GWAS detected variants may not be ever able to explain familial heritability estimates, at least for some traits [9]

Methods

Findings

Discussion

Conclusion