Research question: What offspring health outcomes are associated with an advanced paternal age at birth?
Scientific rationale: There have been many studies supporting the associations between an advanced paternal age and a wide range of offspring medical conditions, including neuropsychiatric or developmental disorders (e.g., autism spectrum disorder, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, and intellectual disability), congenital or genetic disorders (e.g., achondroplasia, and rare structural birth defects), and cancers (e.g., childhood leukemia, and breast cancer). The increased offspring disease risk conferred by an advanced paternal age might be driven by more accumulated de novo mutations, and altered DNA methylation patterns in the sperm, as well as selection bias. However, there is no existing study comprehensively investigating the offspring medical conditions associated with an advanced paternal age. Studies revealing the association patterns of medical conditions for an advanced paternal age can inform parental counseling and early screening strategies, facilitate targeted public health interventions for offspring of older fathers, and provide novel insights into the mechanisms underlying medical conditions associated with paternal age.
Objectives and methods: In this study, we will perform a phenome-wide association study for paternal age at birth with over 600 diseases from 16 disease categories based on data from the UK Biobank. The paternal age will be calculated as: father’s age at initial assessment (p2946_i0) – age when attended assessment centre (p21003_i0). As the information for father’s age is only available for 114,642 participants, we could only perform phenome-wide association study among these over 100,000 participants with available information on paternal age. Diagnoses will be derived from linked health data including primary care, hospital inpatient records, and registers for cancer and deaths.