Rare and Common Variants: Twenty arguments

By Greg Gibson. Nature reviews genetics, 2011

1,260 citations recorded by the source corpus.

Genome-wide association studies have greatly improved our understanding of the genetic basis of disease risk. The fact that they tend not to identify more than a fraction of the specific causal loci has led to divergence of opinion over whether most of the variance is hidden as numerous rare variants of large effect or as common variants of very small effect. Here I review 20 arguments for and against each of these models of the genetic basis of complex traits and conclude that both classes of effect can be readily reconciled.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/2a9f9310a05dafd57c2dc762e08b4a657748405b

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Citations in the corpus

Genomics to systems biology in animal and veterinary sciences: Progress, lessons and opportunities☆ (2014, background): “, 2010) and there were indications that an SNPchip that only has common variants but not rare variants may be the cause of hidden heritability (Gibson, 2012).”
The placebo effect: From concepts to genes. (2015, positive): “The last decade of genome-wide association studies have demonstrated that complex traits are often influenced by a large number of common alleles with very small effect sizes (Gibson, 2012).”
An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis. (2017, background): “The additive contributions of hundreds or thousands of polymorphisms, regulating different biochemical pathways related to the phenotype, determine the genetic liability to complex disorders (1).”
A tutorial on conducting genome‐wide association studies: Quality control and statistical analysis (2018, positive): “The overall picture of these results suggest that psychiatric traits are influenced by many common as well as rare SNPs each having small individual effect sizes (Gibson, 2012).”
The advantages and limitations of trait analysis with GWAS: a review (2013, background): “Because of this both rare variants and small effect size present problems for GWAS [29,30].”
Should evolutionary geneticists worry about higher-order epistasis? (2013, background): “Epistasis is also of critical importance to the analysis of genomewide association data [12,13]”
The Next-Generation Sequencing Revolution and Its Impact on Genomics (2013, neutral): “There are still questions that remain as to whether the genetic contribution to common traits can be attributed to an infinite number of common alleles with small effect, a large number of rare alleles with large effects, or some combination of genes and environment (Gibson, 2011).”
Rare-variant association analysis: study designs and statistical tests. (2014, background): “10 Evolutionary theory predicts that deleterious alleles are likely to be rare as a result of purifying selection, 10,11 and indeed, loss-of-function variants, which prevent the generation of functional proteins, are especially rare.”
The genomics of local adaptation in trees: are we out of the woods yet? (2017, background): “Despite an ongoing debate within the literature (Wright 1932; Whitlock 1995; Crow 2008, 2010; Gibson 2012; Zuk et al. 2012; Hansen 2013; Hemani et al. 2013; Nelson et al. 2013; Mäki-Tanila & Hill 2014; Ávila et al. 2014; Paixão & Barton 2016), and given that there seems to be no general prevalence…”