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Transl Psychiatry. 2020 Jan 21;10(1):23. doi: 10.1038/s41398-019-0676-2.

Genomic prediction of alcohol-related morbidity and mortality.

Author information

1
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
2
Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
3
Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry Massachusetts General Hospital, Boston, MA, USA.
4
The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Boston, MA, USA.
5
Department of Psychiatry, Washington University School of Medicine in St.Louis, St.Louis, MO, USA.
6
Department of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, IN, USA.
7
Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
8
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. samuli.ripatti@helsinki.fi.
9
Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland. samuli.ripatti@helsinki.fi.
10
The Broad Institute of MIT and Harvard, Cambridge, MA, USA. samuli.ripatti@helsinki.fi.

Abstract

While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85-12.58 g, p = 2.3 × 10-58). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66-2.01, p = 1.6 × 10-36). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive baseline data from prospective cohorts, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI = 1.26-1.99, p = 8.2 × 10-5). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI = 1.20-1.47, p = 4.5 × 10-8) in the adjusted model. In conclusion, the PRS for alcohol consumption independently associates for both alcohol-related morbidity and all-cause mortality. Together, these findings underline the importance of heritable factors in alcohol-related health burden while highlighting how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.

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