Testing for an Unusual Distribution of Rare Variants

Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants. Through simulations and analysis of case/control data, we demonstrate good power relative to existing methods that assess the burden of rare variants in individuals.

• Publication year

  2011

• Venue

  PLoS Genetics

• Publication date

  2011-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pgen.1001322PMID 21408211PMCID 3048375
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• The C-alpha test statistic demonstrates good power relative to existing burden tests in simulations and case/control data analysis.

  Confidence 0.90

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• The C-alpha test statistic maintains consistent power when evaluating a target set containing both risk and protective variants by testing the variance rather than the mean.

  Confidence 0.95

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review

• burden tests

  method, baseline

  Existing statistical methods that assess the cumulative effect of rare variants by testing the mean.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• c-alpha test statistic

  method, statistic

  A novel statistical approach that evaluates the variance rather than the mean to detect a mixture of effects across a set of rare variants.

  Aliases: C-alpha

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• case/control data

  data type, evaluation setting

  Genetic data from subjects with a condition and unaffected individuals, used here to evaluate the power of rare variant tests.

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review
• rare variants

  genetic feature

  Genetic variations with very low frequency whose individual influences are evaluated effectively as a group.

  Aliases: rare variation

  All you need is Python (5d7gwfm5zu) extractionAnonymous (12632b8b5f) review

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