DNAprint Genomics (DNAG)

[mingwan0]

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Grant Number: 5U01DK062413-03
PI Name: YANG, HUIYING
PI Email: [e-mail]
PI Title: ASSISTANT PROFESSOR AND ASSOCIATE
Project Title: Mapping genes for IBD by admixture LD in Puerto Ricans

Abstract: DESCRIPTION (provided by applicant): Studies by the genome scan approach have identified over 10 chromosomal regions containing putative loci predisposing to IBD. The identified IBD1 gene (NOD2) can only explain a small percent of Crohn's disease (CD) patients and does not contribute to ulcerative colitis (UC). Thus, other genes that contribute to IBD susceptibility exist and need to be identified. Compared to the NOD2 gene, the remaining loci contribute a lower susceptibility to IBD as indicated by weaker linkage evidence and less consistency across populations/studies. To identify such genes with modest effects, association studies based on linkage disequilibrium (LD) are the method of choice. However, in the Caucasian population the extent and usefulness of LD is limited by population history. Therefore, we herein propose an alternative strategy to map the IBD genes by taking advantage of an admixed population in Puerto Rico - mapping by admixture linkage disequilibrium (MALD). The goal of this study is to identify IBD susceptibility genes by narrowing selected chromosome regions showing sufficient evidence for linkage, then performing fine mapping using both case-control and the family based approaches. Specifically, the investigators will establish a panel of clinically characterized Puerto Rican IBD patients (300UC, 300CD, 300control) and families (400 trios); narrow selected chromosomal regions containing putative loci for IBD using MALD with population specific markers; evaluate potential interaction/confounding effect with NOD2 and serological antibodies (ANCA, ASCA, I2); and fine map the susceptibility genes with dense markers across the narrowed region and within candidate genes. By covering important chromosomal regions, using an admixed population in which LD has been sustained at longer chromosome segments; genotyping sufficient population specific markers; controlling for spurious association; evaluating interaction effects with other factors, and employing a two-stage mapping strategy, this proposal maximizes the opportunity to refine the chromosomal regions that contain susceptibility genes for IBD, thus enhancing the opportunity to identify the actual genes that contribute to the development of IBD.

Thesaurus Terms:
Puerto Rican, gene expression, genetic mapping, inflammatory bowel disease, linkage disequilibrium
chromosome, clinical trial, cooperative study, gene mutation, genetic marker, genetic susceptibility, genotype, quantitative trait loci
clinical research, human subject

Institution: CEDARS-SINAI MEDICAL CENTER BOX 48750, 8700 BEVERLY BLVD LOS ANGELES, CA 900481804
Fiscal Year: 2004
Project Start: 30-SEP-2002
Project End: 30-JUN-2007
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

http://www.csmc.edu/4017.html

Director, Genetics Epidemiology

Huiying Yang, MD, PhD is Director of the Genetic Epidemiology Program for the Medical Genetics Institute at Cedars-Sinai. Dr. Yang is also an associate professor of pediatrics an associate professor of epidemiology at the David Geffen School of Medicine at University of California, Los Angeles (UCLA), and she is a guest professor at the School of Public Health, Peking University, Health Science Center.

Dr. Yang's primary areas of research interest involve genetic and environmental risk factors for several common complex diseases. She leads several National Institutes of Health (NIH)-funded research projects, including projects to: map genes for inflammatory bowel disease in Caucasian populations using linkage and linkage disequilibrium approaches; use a mapping by admixture linkage disequilibrium approach to identify susceptibility genes for inflammatory bowel disease in the Puerto Rican population; study host genetic predisposition which determines an individual's response to interferon-related therapy among HCV infected patients; and map genes for keratoconus. In addition, she leads analytic efforts in two other multi-center projects - a program project of mapping genes for insulin resistance in a Mexican-American population, and a pharmacogenetics study of ACE inhibitors and statins in Caucasian and African-American populations.

Dr. Yang is a member of numerous professional organizations, including the American Society of Human Genetics, Society for Epidemiologic Research, International Epidemiological Association, International Genetic Epidemiology Society, American Gastroenterological Association and the American Diabetes Association. She has served on several NIH-sponsored research steering committees and has published numerous genetic epidemiology research reports and review articles.

After graduating from Beijing Medical University (now Peking University, Health Science Center), she started her postgraduate training in genetic epidemiology with Drs. C.S. Chung and Newton Morton at the University of Hawaii. When she completed her doctorate degree program, she started postdoctoral training at the Medical Genetics Institute at Cedars-Sinai.