Safe linkage of cohort and population-based register data in a genome-wide association study on health care expenditure

Abstract

AbstractBackgroundThere are research questions whose answers require record linkage of multiple databases which may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run analyses in a high performance computing (HPC) environment.MethodsAfter successful record linkage genome-wide association (GWA) analyses were carried out on expenditure for total health, mental health, primary and hospital care and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and SNP-based heritability.ResultsThe total heritability of expenditure ranged between 29.4 (SE 0.8) and 37.5 (SE 0.8) per cent, but GWA analyses did not identify single SNPs or genes that were genome-wide significantly associated with health care expenditure. SNP-based heritability was between 0.0 (SE 3.5) and 5.4 (SE 4.0) per cent and was different from zero for mental health care and primary care expenditure.ConclusionsWe successfully linked genotype data to administrative health care expenditure data from Statistics Netherlands and performed a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analysing linked data in large-scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.Key messagesCohort data of the Netherlands Twin Register were safely linked to population-based register data of Statistics NetherlandsOn the ODISSEI Secure Supercomputer (OSSC) platform genome-wide association analyses were carried out on linked genotype and health care expenditure dataVariation in health care expenditure was for approximately one third explained by family-based heritability, but SNP-heritability based on genetic similarity across unrelated individuals explained only a very small proportion of varianceThe newly developed platform can serve as a prototype for realizing genome-wide association studies with sensitive data