Abstract / Summary
Sex and gender are distinct but intertwined determinants of health. Both adherence to and deviation from gender norms carry consequences for health, yet gender's contribution to disease risk beyond binary sex remains largely unexplored. As gender is organized around sex from its developmental origins, masculine and feminine health behaviors can be defined by how males and females behave collectively. Individuals vary in how closely they align with these norms, defining a biopsychosocial gender spectrum. Here, we used machine learning to reconstruct population-specific masculine and feminine behavioral norms, yielding a continuous Index of Gendered Life-domains (IGL) in 301,113 UK Biobank participants. In sex-stratified analyses of body and brain health phenotypes, masculine behavioral profiles were associated with greater physiological load and cardiometabolic disease risk, and feminine profiles with higher trait anxiety and musculoskeletal vulnerability. Sex-IGL incongruence predicted state-like psychiatric symptoms and severe mental health diagnoses. An intersectional approach revealed differences in gendered behaviors and their health associations across ethnic groups, demonstrating that gender measurement must be sensitive to sociocultural context to characterize health risk in diverse populations. These findings establish gender as a socioculturally embedded determinant of health whose health associations go beyond binary sex.