Missing heritability, polygenic scores, and gene–environment correlation
نویسنده
چکیده
This special issue amply fulfils its aim of moving the study of gene × environment (GE) interplay forward constructively and creatively, exploiting contributions from diverse disciplines. Rather than discussing the many interesting findings and methods in this special issue, I will comment on two cross-cutting issues - one about genes and the other about the environment - that came to mind as I read these articles.
منابع مشابه
Predictive accuracy of combined genetic and environmental risk scores
The substantial heritability of most complex diseases suggests that genetic data could provide useful risk prediction. To date the performance of genetic risk scores has fallen short of the potential implied by heritability, but this can be explained by insufficient sample sizes for estimating highly polygenic models. When risk predictors already exist based on environment or lifestyle, two key...
متن کاملMeta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies
Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy...
متن کاملRevisiting the Polygenic Additive Liability Model through the Example of Diabetes Mellitus.
Most studies on multifactorial diseases are performed under the assumption of a polygenic additive liability. In particular, missing heritability and individual risk scores are estimated under this model. In this paper, we use the example of diabetes to highlight the pitfalls of relying on such a model, when there are reasons to suspect etiological heterogeneity and/or departure from the hypoth...
متن کاملTandem repeat polymorphisms: modulators of disease susceptibility and candidates for 'missing heritability'.
A problem of 'missing heritability' has been identified following recent genome-wide association (GWA) studies of single nucleotide polymorphisms (SNPs) associated with complex diseases. Current GWA studies fail to detect key sources of genetic variation, particularly tandem-repeat polymorphisms (TRPs), which provide a unique source of genetic variability by modulating a range of biological pro...
متن کاملFine mapping genetic associations between the HLA region and extremely high intelligence
General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely power...
متن کامل