Computer Science Colloquium
Time+Place : Tuesday 10/01/2012 14:30 room 337-8 Taub  Bld.

Speaker    : Or Zuk
Affiliation: Broad Institute of MIT and Harvard

Host       : Dan Geiger

Title      : Missing Heritability: New algorithmic and statistical
Abstract   :
The completion of the human genome project set a stepping stone in building
catalogs of common human genetic variation. These catalogs, in turn, enabled
the search for associations between common variants and complex human traits
and diseases, by performing Genome-Wide Association Studies (GWAS). GWAS
have been successful in discovering thousands of statistically significant,
reproducible, genotype-phenotype associations. However, the discovered
variants (genotypes) explain only a small fraction of the phenotypic
variance in the population for most human traits.  In contrast, the
heritability, defined as the proportion of phenotypic variance explained by
all genetic factors, was estimated to be much larger for those same traits
using indirect population-based estimators. This gap is referred to as
'missing heritability'.
Mathematically, heritability is defined by considering a function $F$
mapping a set of (Boolean) variables, $(x_1,.., x_n)$ representing
genotypes, and additional environmental or 'noise' variables $\epsilon$, to
a single (real or discrete) variable $z$, representing phenotype. We use the
variance decomposition of $F$, separating the linear term, corresponding to
additive (narrow-sense) heritability, and higher-order terms, representing
genetic-interactions (epistasis), to explore several explanations for the
'missing heritability' mystery. We show that genetic interactions can
significantly bias upwards current population-based heritability estimators,
creating a false impression of 'missing heritability'. We offer a solution
to this problem by providing a novel consistent estimator based on unrelated
individuals. We also use the Wright-Fisher process from population genetic
theory to develop and apply a novel power correction method for inferring
the relative contributions of rare and common variants to heritability.
Finally, we propose a novel algorithm for estimating the different variance
components (beyond additive) of heritability from GWAS data.
I will give the needed genetics background, and discuss the statistical
methods and algorithms used.
Short Bio:
I am currently a post-doc at the Broad Institute of MIT and Harvard, in Eric
Lander's lab. I work on computational and statistical problems arising from
genomics applications, in particular in human genetics and comparative
I have completed my Ph.D. in Computer Science and Applied Mathematics at the
Weizmann Institute of Science under the supervision of Eytan Domany.
Refreshments served from 14:15 on,
 	Lecture starts at 14:30
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