Webcast: Using Runs of Homozygosity to Identify Recessive Loci

Presenter: Todd Lencz, PhD., Zucker Hillside Hospital, Feinstein Institute for Medical Research

Date: January 24, 2008

Duration: 60 Minutes

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Abstract

The recent development of microarray platforms, capable of genotyping hundreds of thousands of single nucleotide polymorphisms (SNPs), has provided an opportunity to rapidly identify novel susceptibility genes for complex phenotypes. Studies employing genotyping microarrays have typically utilized a whole genome association (WGA) approach, in which each SNP is examined individually for association with disease. While this approach has resulted in several important breakthroughs in the past two years, it is biased towards detecting common alleles with additive effects. At the same time, structural properties of WGA datasets, including patterns of linkage disequilibrium (LD), have not yet been exploited in these analyses.

Consequently, we developed a novel analytic approach termed whole genome homozygosity association (WGHA). WGHA first identifies patterned clusters of SNPs demonstrating extended homozygosity (runs of homozygosity or "ROHs") and then employs both genomewide and regionally-specific statistical tests for association to disease. This approach can identify chromosomal segments that may harbor rare, penetrant recessive loci. We have recently utilized WGHA in a case-control dataset of patients with schizophrenia and healthy volunteers, genotyped at ~500,000 SNPs, and detected several novel susceptibility loci for schizophrenia. In this webinar, we will address the theoretical and statistical underpinnings of WGHA, its implementation in HelixTree software, and its potential utility in studies of complex disease.

About the Presenter

Dr. Todd Lencz is an Assistant Professor of Psychiatry at the Albert Einstein College of Medicine, Assistant Investigator in the Feinstein Institute for Medical Research at NS-LIJHS, and Senior Psychologist at the Zucker Hillside Hospital (ZHH). He serves as Associate Director for the Recognition and Prevention (RAP) Program, as well as the Unit of Molecular Psychiatry in the Department of Psychiatry Research at ZHH. Dr. Lencz received his B.A. in Psychology (Magna cum Laude with Distinction in the Major) from Yale University and Ph.D. in Clinical Psychology from the University of Southern California, where he won the Distinguished Dissertation Award.

Dr. Lencz is the author or co-author of nearly 50 peer-reviewed scientific publications, focusing on three related research projects in the biology of schizophrenia and other serious mental illness:

1. refining the clinical criteria (phenotype) that define the boundaries of mental illness;
2. identifying endophenotypic markers of mental illness in the brain, using techniques such as magnetic resonance imaging (MRI) and neurocognitive testing;
3. using molecular genetics to characterize risk genotypes.

Dr. Lencz is also the recipient of a Career Development Award from the National Institute of Mental Health, a Young Investigator Award from the National Alliance for Research on Schizophrenia and Affective Disorders, and is the first awardee of the KeySpan Industries Medical Research Fellowship. Dr. Lencz is also co-editor of the book Schizotypal Personality, published by Cambridge University Press.