We utilized a cohort of 132,113 male and female research participants of European ancestry. All participants were drawn from the customer base of 23andMe, Inc., a direct-to-consumer genetics company. Participants provided informed consent and participated in the research online, under a protocol approved by the external AAHRPP-accredited IRB, Ethical & Independent Review Services (www.eandireview.com). During 4 months in 2015 and 14 months in 2018–2020, participants responded to a decision-making survey that, depending on branching logic, included up to 139 questions pertaining to aspects of impulsivity and substance use and abuse. A single item in this survey asked, “Have you ever in your life used prescription painkillers (taken not as prescribed), e.g., Vicodin, Oxycontin?”. A total of 132,113 individuals responded, with 27,805 (10,164 males) answering ‘yes’ (cases) and the remaining 104,308 (36,246 males) answering ‘no’ (controls). Controls were not screened for prior opioid use, so they represent a combination of individuals who have taken opioids but only as prescribed, and others who have never taken an opioid. Only individuals who were categorized as being of European ancestry based on empirical genotype data [15] were included in this study. Demographic information about this sample is presented in Supplementary Table 1.
