The effect of genetic predisposition to Alzheimer's disease and related traits on recruitment bias in study of cognitive ageing

The recruitment of participants for research studies may be subject to bias due to an overrepresentation of those more willing to participate voluntarily. No study has analysed the effect of genetic predisposition to Alzheimers disease (AD) on study participation. The Prospective Imaging Study of Ageing (PISA), aims to characterise the phenotype and natural history of healthy adult Australians at high future risk of AD. PISA participants were recruited from existing cohort studies with available genome-wide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment. From a recruitment pool of 13,432 individuals (age 40-80), 64% of participants were successfully recruited into the study. Polygenic risk scores (PRS) were computed in order to test to what extent the genetic risk for AD, and related risk factors (including educational attainment, household income and IQ), predicted participation in PISA. We examined the associations between PRS and APOE ε4 with recruitment using logistic regression models. We found significant associations of age and sex with study participation, where older and female participants were more likely to complete the core module. We did not identify a significant association of genetic risk for AD with study participation. Nonetheless, we identified significant associations with genetic scores for key causal risk factors for AD, such as IQ, household income and years of education. Our findings highlight the importance of considering bias in key risk factors for AD in the recruitment of individuals for cohort studies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The Prospective Imaging Study of Ageing (PISA) is funded by the National Health and Medical Research Council (Grant ID: APP1095227). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted by the Human Research Ethics Committees (HREC) of QIMR Berghofer Medical Research Institute. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors