American Statistical Association
New York City
Metropolitan Area Chapter

Mailman School of Public Health
Columbia University
Department of Biostatistics Colloquium



ANALYSIS AND REPLICATION OF
COMPLEX TRAIT RARE VARIANT ASSOCIATION STUDIES:
APPLICATION TO NEXT GENERATION SEQUENCE DATA

by

Suzanne Leal, Ph.D.
Department of Medicine & Human Genetics
Baylor College of Medicine
www.bcm.edu/genetics/?pmid=10939


Abstract

There is overwhelming evidence that rare variants play an important role in complex disease etiology. Although published rare variant association studies have been limited to a few complex trait candidate gene studies, currently many studies are generating exome sequence data using second-generation sequencing in order to detect rare variant complex trait associations. Association methods used to analyze common variants should not be used for the analysis or rare variants since they are grossly underpowered. Instead, methods which have been developed to test for association with rare variants which rely on aggregating information on rare variants within a region, e.g. gene should be used. Once associations are detected, it is important to replicate the findings in an independent sample, since findings can be false positives even if the family wise error rate is well controlled. Additionally spurious associations can occur due to improperly controlling for population admixture/substructure and sequencing errors. Methods to analyze rare variant association data for complex traits will be presented and their power will be compared for a variety of underlying genetic models. Additionally strategies for gene-based replication will be compared in particular whether variant-based replication is sufficiently powered or sequence-based replication is necessary.

Biographical Note

Suzanne M. Leal, Ph.D. is currently a Professor in the Department of Molecular and Human Genetics and Director of the Center for Statistical Genetics at Baylor College of Medicine. She received a Master of Science degree in Biostatistics in 1989 and a Doctor of Philosophy degree in Epidemiology in 1994 from Columbia University. Suzanne’s interest in statistical genetics lies in methodological research and in recent years the emphasis of this work has been developing methods to detect rare variant associations for complex traits using sequence data. She is also interested in applied work, mapping susceptibility genes for complex and Mendelian traits, which includes studies on nonsyndromic hearing impairment, pain perception, platelet reactivity and coronary disease. Suzanne is interested in education and in addition to mentoring pre- and post-doctoral fellows she teaches courses in statistical genetics in the United States and internationally. She is currently on the IGES board of directors and is an associate editor for the American Journal of Human Genetics and PLoS Genetics.


Date: Thursday, March 31, 2011
Time: 4:00 - 5:00 P.M.
Location: Mailman School of Public Health
Department of Biostatistics
722 West 168th Street
Biostatistics Computer Lab
6th Floor - Room 656
New York, New York

RESERVATIONS ARE NOT REQUIRED

Informal tea at 3:40 P.M.


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