Searching for missing heritability: Designing rare variant association studies

By Or Zuk, S. Schaffner, Kaitlin E. Samocha, R. Do, Eliana Hechter, Sekar Kathiresan, Mark J. Daly, Benjamin M. Neale, Shamil R. Sunyaev, Eric S. Lander. Proceedings of the National Academy of Sciences of the United States of America, 2014

633 citations recorded by the source corpus.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0a76382087777058b862c7149df31c29bbb37f58

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Psychiatric Genomics: An Update and an Agenda (2017, background): “Rare variant studies have proven more difficult than anticipated, because to confidently identify rare variants of strong effect in typical clinical samples requires very large sample sizes, perhaps as many as around 100,000 cases (38).”
Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects (2016, neutral): “These rare variants also include many variants with large effect sizes, which are targets of disease-sequencing studies 7 .”
Using high-resolution variant frequencies to empower clinical genome interpretation (2016, background): “6,7 It is intuitively apparent that when assessing a variant for a causative role in a dominant Mendelian disease, the frequency of a variant in a reference sample, not selected for the condition, should not exceed the prevalence of the condition.”
The Ensembl Variant Effect Predictor (2016, background): “WGS in large numbers of samples is required to yield enough statistical power to detect rare variants with potential phenotypic or disease associations (Pierre and Génin 2014; Zuk et al. 2014).”
Rare-variant association analysis: study designs and statistical tests. (2014, methodology): “117,118 Note that we could capture a higher fraction of heritability if we used more powerful gene-or region-based tests instead of a single-variant test, but the overall qualitative conclusion would be similar.”