Dissecting the genetics of nausea symptoms and their relationship with related traits.
Approved Research ID: 75072
Approval date: May 24th 2022
Nausea is a commonly encountered symptom with a broad list of possible causes including migraine, pregnancy loss, diseases of gastrointestinal tract (gastroesophageal reflux disease, peptic ulcer disease), blood glucose levels, alcohol consumption, heart attack, hepatic failure, motion sickness, meningitis, chemotherapy. The underlying mechanisms involved in nausea are complex and encompass psychological states, the central nervous system, autonomic nervous system, gastric dysrhythmias, and the endocrine system. For example, symptoms of nausea and vomiting, experienced by ~70% of pregnant women, usually occur in the first trimester of pregnancy, and are related to risk of pregnancy loss /miscarriage, maternal morbidity and adverse birth outcomes. The pathogenesis of nausea and related conditions is multifactorial, the genetics being the least studied. Identification of the predisposing new gene(s) may help in determining the cause (risk factors) of this poorly understood condition and to facilitate development of novel therapeutics and more individualized health interventions.
We estimate duration of our project 36 months. This project will provide insights into the genetics of nausea symptoms, a phenotype that has been widely neglected before. We will dissect for the first time in a well-powered study the relationship and causality between nausea, other traits, such as miscarriage, where nausea is a symptom and metabolite levels.
The unique methodology, we plan to apply in this project, will enable dissecting, first, the shared genetics between nausea and other conditions and might suggest pleiotropic effects, and second, causality of relationships between phenotypes of our interest. Since nausea is a symptom in multiple traits, such as migraine, postoperative conditions (anaesthesia), risk factor for pregnancy loss, liver failure, heart attack, medications, for example chemotherapy, motion sickness and seasickness, alcohol use, low blood sugar etc., we will dissect such multi-phenotype effects in our analysis. Our findings will be useful not only for basic science, but also for clinical research, since it is important to dissect whether nausea is truly among causes of different conditions. We will also evaluate the role of coding mutations influencing susceptibility to nausea symptoms, which might enlighten additional genes involved in pathophysiology of nausea and this will open new avenues for prevention of this condition and ways for development of innovative medicines.