Genetic risk factors have a substantial impact on healthy life years

Sakari Jukarainen; Tuomo Kiiskinen; Sara Kuitunen; Aki S Havulinna; Juha Karjalainen; Mattia Cordioli; Joel T Rämö; Nina Mars; FinnGen; Kaitlin E Samocha; Hanna M Ollila; Matti Pirinen; Andrea Ganna

doi:10.1038/s41591-022-01957-2

Genetic risk factors have a substantial impact on healthy life years

Nat Med. 2022 Sep;28(9):1893-1901. doi: 10.1038/s41591-022-01957-2. Epub 2022 Sep 12.

Authors

Sakari Jukarainen¹, Tuomo Kiiskinen^{2

3

4}, Sara Kuitunen^{2

3}, Aki S Havulinna^{2

3}, Juha Karjalainen^{2

4

5}, Mattia Cordioli², Joel T Rämö², Nina Mars²; FinnGen; Kaitlin E Samocha^{4

6}, Hanna M Ollila^{2

4

6

7}, Matti Pirinen^{2

8

9}, Andrea Ganna^{10

11

12}

Affiliations

¹ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. sakari.jukarainen@helsinki.fi.
² Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
³ Finnish Institute for Health and Welfare, Helsinki, Finland.
⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁶ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁷ Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁹ Helsinki Institute for Information Technology HIIT and Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
¹⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. andrea.ganna@helsinki.fi.
¹¹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. andrea.ganna@helsinki.fi.
¹² Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. andrea.ganna@helsinki.fi.

Abstract

The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Global Burden of Disease*
Global Health
Health Status
Humans
Male
Quality-Adjusted Life Years
Risk Factors
Sodium, Dietary*

Substances

Sodium, Dietary