Proceedings of the 2017 International Conference of Precision Health and Precision Nutrition
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MEETING ABSTRACTS
Open Access
Proceedings of the 2017 International Conference of Precision Health and Precision Nutrition Shanghai, China. 6-7 November 2017 Published: 9 May 2018
Session I Big cohorts, big data, and precision health S1 Mendelian randomization, molecular mediation to understand and prioritize for interactive targets in populations of diverse ethnicities Simin Liu1,2 1 Brown University School of Public Health, Providence, RI, USA; 2Alpert School of Medicine, Providence, RI, USA Nutrition & Metabolism 2018, 15(Suppl 1):S1 One fundamental principle of biology is interaction, understanding of which forms the basis for the development of novel therapeutic and preventive strategies with proven clinical efficacy (Phase III) and population effectiveness (Phase IV and implementation). The existing research and implementation processes for both drug therapy and new diagnostic tools are very fragmented and grossly insufficient. First, the drug development process takes too long (1015 years/drug) and cost too much (~$1 billion/drug) with high failure rates (~80%) even for targets and compounds that survive through Phases II development. Second, the lack of assessment for interactions among genetic factors and therapeutic agents in almost all human studies may be a rate-limiting step for success (or lead to post-marketing failure due to as yet unknown off-target detrimental effect). Third, current structure does not encourage basic scientists to work closely with clinical and population scientists. Last and most importantly, insufficient measurement of covariates often precludes from confidently predicting intermediate or long-term effects of various agents. I propose here that by applying innovative systems biology approaches to existing cohort resources, the biological pathways and gene networks that are perturbed by genetic variations and their interactions with potential targets and phenotypic risks could be modeled in both the preclinical and post-marketing period to evaluate potential benefits and risks associated with both new drugs and/or targets. We have recently used this unique and comprehensive approach in assessing biological targets in relation to risk of developing type 2 diabetes (T2D) and cardiovascular complications among T2D patients in diverse ethnic populations. Herein I use several examples to demonstrate that such a strategy should be adopted in the drug (including nutritional supplements) development process to enhance the probability of discovery and validation of targets, thus reducing wasteful resources. To complement this unbiased approach, we will also focus the sex-steroid pathway recently identified including sex-hormone binding globulin (SHBG) as therapeutic targets for enhancing or impairing insulin sensitivity, metabolic syndrome and type 2 diabetes risk particularly concerning multiple germline mutations in the sexhormone pathways as well as the SHBG gene to be predictive of both metabolic syndrome and T2D risk in multiple cohorts of men and women.
S2 Study for precision m
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