Safe Linkage of Cohort and Population-Based Register Data in a Genomewide Association Study on Health Care Expenditure

Abstract

There are research questions whose answers require record linkage of multiple databases that 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 large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study 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 single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.

Evaluating the causal relationship between educational attainment and mental health

“…Mental health care expenditures 64 are assessed in two ways: expenditures from the first line/basic care and expenditures from the 2nd line/specialized care. We summed basic and specialized care for each year.…”

“…Regarding ASD, we consider a definition closer to the DSM V (spectrum), also used for the GWAS, including patients with: autistic disorder, Mental health care expenditures64 are assessed in two ways: expenditures from the first line/basic care and expenditures from the 2nd line/specialized care. We summed basic and specialized care for each year.…”

Quantifying the causal impact of biological risk factors on healthcare costs

“…We performed validation analyses in the UK Biobank 10 ( N = 307,048) and Netherlands Twin Register 43 ( N = 16,726) to evaluate the generalizability and robustness of our results to different healthcare systems in different countries. For the UK Biobank, annual total healthcare costs were used as the primary outcome, in which pounds were converted to euros using the average exchange rate in 2021 of 1 EUR = 0.8403 GBP, and in-house GWAS protocols for quality control were used 44 .…”

Quantifying the causal impact of biological risk factors on healthcare costs

“…We performed validation analyses in the UK Biobank 23 (N=307,048) and Netherlands Twin Register 24 (N=16,726) to evaluate the generalizability and robustness of our results to different healthcare systems in different countries. For the Netherlands Twin Register, we used published GWAS summary statistics 24 . For UK Biobank, we expand upon published analyses for BMI 23 .…”