AbstractResponse to survey questionnaires is vital for social and behavioural research, and most analyses assume full and accurate response by participants. However, nonresponse is common and impedes proper interpretation and generalizability of results. We examined item nonresponse behaviour across 109 questionnaire items in the UK Biobank (N = 360,628). Phenotypic factor scores for two participant-selected nonresponse answers, ‘Prefer not to answer’ (PNA) and ‘I don’t know’ (IDK), each predicted participant nonresponse in follow-up surveys (incremental pseudo-R² = 0.056), even when controlling for education and self-reported health (incremental pseudo-R² = 0.046). After performing genome-wide association studies of our factors, PNA and IDK were highly genetically correlated with one another (r_g = 0.73 (s.e. = 0.03)) and with education (r_g,PNA = −0.51 (s.e. = 0.03); r_g,IDK = −0.38 (s.e. = 0.02)), health (r_g,PNA = 0.51 (s.e. = 0.03); r_g,IDK = 0.49 (s.e. = 0.02)) and income (r_g,PNA = –0.57 (s.e. = 0.04); r_g,IDK = −0.46 (s.e. = 0.02)), with additional unique genetic associations observed for both PNA and IDK (P < 5 × 10⁻⁸). We discuss how these associations may bias studies of traits correlated with item nonresponse and demonstrate how this bias may substantially affect genome-wide association studies. While the UK Biobank data are deidentified, we further protected participant privacy by avoiding exploring non-response behaviour to single questions, assuring that no information can be used to associate results with any particular respondents.