A Candidate Gene Association Study Of Irritable Bowel Syndrome
Saitoloftus, Yuri A
Mayo Clinic Coll Of Medicine, Rochester
Grant 1R03DK076797-01A2 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK
Abstract: Irritable bowel syndrome (IBS) is a common chronic disorder that results in high health care expenditures, disability, and decreased quality of life. Dr. Yuri Ann Saito-Loftus´ long term objective is to understand the pathophysiology of this disorder so that better tests and treatments may be discovered. Her K23 Mentored Patient-Oriented Research Career Development Award utilizes a family case-control study design to collect evidence for whether there is a genetic basis for IBS. This application proposes to supplement the K23 study by accomplishing two additional specific aims using data and DNA collected from the K23 study. Because serotonin and serotonin-related proteins have been implicated in the pathophysiology of IBS, we propose performing a pathway-based candidate-gene association study to determine whether genetic variants in genes encoding serotonin-related molecules are associated with IBS. Using our institution´s high-throughput genotyping resources, 384 linkage disequilibrium (LD) tag SNPs in 22 serotonin pathway genes will be genotyped in 645 cases and 323 controls, and IBS subgroups will be analyzed to determine whether there is evidence for genetic heterogeneity for this clinically heterogeneous disorder. A candidate gene association study of this type and scale has not been performed to date and could provide specific genes and molecular targets for future study. PUBLIC HEALTH RELEVANCE Irritable bowel syndrome (IBS) is a common chronic disorder that results in high health care expenditures and disability because the underlying mechanism is unknown. The broad objective of this study is to identify specific genes and molecular targets for future study so that better tests and treatments may be developed. With this study, we propose using collected DNA and our institution´s high-throughput genotyping resource to study the genome to determine whether there are regions that may contain genetic variants or mutations responsible for IBS
Project start date: 2008-04-01
Project end date: 2010-03-31
1R03DK076797-01A2 (2008): $75550
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Saitoloftus, Yuri A
Genetic Epidemiology Of Irritable Bowel Syndrome (IBS)
Saitoloftus, Yuri A
Mayo Clinic Coll Of Medicine, Rochester
Grant 5K23DK066271-05 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK
Abstract: Yuri Ann Saito s long-term research objective is to understand the pathophysiology of functional gastrointestinal disorders so that effective treatments may be found for this common disorder that affects 10- 20% of the population. She believes that this can be achieved in part through the use of advanced epidemiological methods. The K23 Mentored Patient-Oriented Research Career Development Award would provide an excellent opportunity to gain experience in conducting high-quality epidemiological and genetic epidemiological research in functional gastrointestinal diseases. The proposed research plan is targeted toward expanding our basic understanding of why irritable bowel syndrome (IBS) appears to cluster in families, and to evaluate the environmental and possible genetic factors contributing to IBS. A combined case-control and family study is proposed where questionnaire data will be collected from 500 clinic-based patients with IBS, 500 clinic-based controls, and approximately 5000 first-degree relatives. The aims of this study are geared to answer whether IBS truly aggregates in families, what are the characteristics of familial IBS, and whether IBS transmission in families follows a genetic pattern. Thus, this study composed of 3 complementary sections a familial aggregation study, classification regression tree (CART) analysis to identify clinical and epidemiological features of familial IBS, and complex segregation analysis to determine whether there is evidence of a major gene for IBS. This study s significance is that it will provide meaningful scientific data that would justify future genetic studies including a more extended biospecimen-based study with a search for candidate genes. The study will also provide insight into the non-genetic factors that lead to IBS and its variable manifestations. This career award would build upon her previous experience using survey-based data to study clinic patients and the community and her M.P.H. It would allow her to obtain training in genetic epidemiology, statistical genetics, and genetics through coursework, attending seminars, and through the project itself at an institution rich in clinical and epidemiological research resources. The additional training and the data generated from this research career development award would ensure that she would advance her academic career, successfully compete for independent peer-reviewed funding, and make significant scientific contributions to the understanding of this and other gastrointestinal disorders.
Keywords: genetic susceptibility, irritable bowel syndrome, patient oriented research, disease /disorder etiology, disease /disorder onset, environmental health, family genetics, gene environment interaction, psychosomatic disorder, clinical research, human subject, postdoctoral investigator, questionnaire, statistics /biometry
Project start date: 2004-03-01
Project end date: 2009-02-28
5K23DK066271-05 (2008): $125820