The mystery of missing heritability: Genetic interactions create phantom heritability

By Or Zuk, Eliana Hechter, Shamil R. Sunyaev, Eric S. Lander. Proceedings of the National Academy of Sciences of the United States of America, 2012

1,592 citations recorded by the source corpus.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1356ff3f147f5fc432c04cc824a4bb8010cf74a1

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Citations in the corpus

Depression sum-scores don’t add up: why analyzing specific depression symptoms is essential (2015, background): “A symptom-based approach offers opportunities for future research that could provide a potential partial explanation for the “mystery of missing heritability” [30] – the conundrum that specific genetic markers explain only small proportions of the variance even for mental disorders that are highly h”
The genomics of local adaptation in trees: are we out of the woods yet? (2017, background): “…been put forth to explain the missing heritability, such as epistasis (Hemani et al. 2013) and its inflationary effect on heritability estimates (Zuk et al. 2012), environmental or epigenetic interactions (Feldman & Lewontin 1975) as well as their inflationary effect on heritability estimates…”
Systems genetics approaches to understand complex traits (2013, background): “However, in such global mapping studies, the identification of interactions at multiple loci is difficult because of the low significance threshold that results from multiple comparisons 54 .”
Inaugural Article: Epistasis dominates the genetic architecture of Drosophila quantitative traits (2012, positive): “, heritability caused by only the additive component of genetic variance) because of genetic interactions in human studies could lead to substantial underestimates of heritability explained by DNA variants (6).”
Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group (2013, background): “Specific genetic variants affecting cognition or disease risk have been hard to identify as their individual effects are small, leaving much of the genetic effect unaccounted for, leading to “missing heritability” (Zuk et al., 2012).”
Genome evolution across 1,011 Saccharomyces cerevisiae isolates (2018, neutral): “The difference between the estimated genome-wide heritability and explained phenotypic variance gives an overview of the extent of missing heritability 48,49 .”
Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems (2016, background): “Complex traits arise from a landscape of genetic variants and mutations, where it is often challenging to interpret the effects of individual genes due to many multi-gene interactions (Kim and Przytycka, 2012; Zuk et al., 2012).”
Rare-variant association analysis: study designs and statistical tests. (2014, background): “8,9 Because GWASs focus on the identiﬁcation of common variants, it is plausible that analyses of low-frequency (0.5% % MAF 5”