Birth defects pose a significant global public health challenge, markedly increasing morbidity and mortality across all stages of life. These conditions arise from complex interactions among genetic susceptibility, environmental exposures, and epigenetic modifications. Beyond adversely affecting early-life health, birth defects also heighten the risk of chronic disorders such as neurodevelopmental impairments, and metabolic abnormalities, thereby diminishing overall quality of life. Despite research advances, a comprehensive understanding of the pathogenesis of birth defects and their associated comorbidities remains limited.
This study aims to systematically explore the multi-omics characteristics of birth defects and their implications for health outcomes throughout the lifespan. Specifically, it will:
(1) utilize a case-control design to investigate the roles of environmental factors (e.g., maternal health, diet, lifestyle, psychosocial determinants, medication use, and viral infections) and genetic factors in the onset and progression of birth defects (e.g., congenital heart disease, Down syndrome, spina bifida, and polydactyly), with an emphasis on developing and applying polygenic risk scores; and (2) examine gene-environment interactions to elucidate the specific relationships among birth-defect-related conditions (e.g., neurodevelopmental disorders, metabolic abnormalities, and immune dysfunction), clinical indicators (e.g., imaging data, serum markers, proteomics, cognitive and neurodevelopmental assessments, electrocardiograms/phonocardiograms, and sleep questionnaires), and environmental factors.
The study will leverage the extensive resources of the UK Biobank, including genomic, transcriptomic, and metabolomic datasets, to identify key molecular mechanisms and modifiable risk factors. The findings will deepen our understanding of the pathophysiological underpinnings of birth defects, informing early diagnostics and effective preventive strategies.
