Objectives To develop a brief, reliable and valid instrument to screen psychosocial risk among those who are undergoing genetic testing for Adult-Onset Hereditary Disease (AOHD).

Design A prospective two-phase cohort study.

Setting 5 genetic testing centres for AOHD, such as cancer, Huntington's disease or haemochromatosis, in ambulatory clinics of tertiary hospitals across Canada.

Participants 141 individuals undergoing genetic testing were approached and consented to the instrument development phase of the study (Phase I). The Genetic Psychosocial Risk Instrument (GPRI) developed in Phase I was tested in Phase II for item refinement and validation. A separate cohort of 722 individuals consented to the study, 712 completed the baseline package and 463 completed all follow-up assessments. Most participants were female, at the mid-life stage. Individuals in advanced stages of the illness or with cognitive impairment or a language barrier were excluded.

Interventions Phase I: GPRI items were generated from (1) a review of the literature, (2) input from genetic counsellors and (3) phase I participants. Phase II: further item refinement and validation were conducted with a second cohort of participants who completed the GPRI at baseline and were followed for psychological distress 1-month postgenetic testing results.

Primary and secondary outcome measures GPRI, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Brief Symptom Inventory (BSI) and Impact of Event Scale (IES).

Results The final 20-item GPRI had a high reliability—Cronbach's α at 0.81. The construct validity was supported by high correlations between GPRI and BSI and IES. The predictive value was demonstrated by a receiver operating characteristic curve of 0.78 plotting GPRI against follow-up assessments using HAM-D and HAM-A.

Conclusions With a cut-off score of 50, GPRI identified 84% of participants who displayed distress postgenetic testing results, supporting its potential usefulness in a clinical setting.