Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan

Saori Sakaue^#^{1

2

3}, Masahiro Kanai^#^{1

2

4

5

6

7

8}, Juha Karjalainen^{4

5

6

8}, Masato Akiyama^{1

9}, Mitja Kurki^{4

5

6

8}, Nana Matoba¹, Atsushi Takahashi^{1

10}, Makoto Hirata¹¹, Michiaki Kubo¹², Koichi Matsuda¹³, Yoshinori Murakami¹⁴; FinnGen; Mark J Daly^{4

5

6

8}, Yoichiro Kamatani^{1

15}, Yukinori Okada^{16

17

18}

Affiliations

¹ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
³ Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁶ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁷ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁸ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁹ Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.
¹⁰ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Japan.
¹¹ Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹² RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹³ Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
¹⁴ Division of Molecular Pathology, Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan.
¹⁵ Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
¹⁶ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.
¹⁷ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.
¹⁸ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.

^# Contributed equally.

PMID: 32251405
DOI: 10.1038/s41591-020-0785-8

Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan

Saori Sakaue et al. Nat Med. 2020 Apr.

. 2020 Apr;26(4):542-548.

doi: 10.1038/s41591-020-0785-8. Epub 2020 Mar 23.

Authors

Affiliations

¹ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
³ Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁶ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁷ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁸ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁹ Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.
¹⁰ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Suita, Japan.
¹¹ Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹² RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹³ Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
¹⁴ Division of Molecular Pathology, Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan.
¹⁵ Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
¹⁶ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.
¹⁷ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.
¹⁸ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.

^# Contributed equally.

PMID: 32251405
DOI: 10.1038/s41591-020-0785-8

Abstract

While polygenic risk scores (PRSs) are poised to be translated into clinical practice through prediction of inborn health risks¹, a strategy to utilize genetics to prioritize modifiable risk factors driving heath outcome is warranted². To this end, we investigated the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (n_total = 675,898; BioBank Japan (n = 179,066), UK Biobank (n = 361,194) and FinnGen (n = 135,638)). In contrast to observational studies, in which discerning the cause-and-effect can be difficult, PRSs could help to identify the driver biomarkers affecting human lifespan. A high systolic blood pressure PRS was trans-ethnically associated with a shorter lifespan (hazard ratio = 1.03[1.02-1.04], P_meta = 3.9 × 10^-13) and parental lifespan (hazard ratio = 1.06[1.06-1.07], P = 2.0 × 10^-86). The obesity PRS showed distinct effects on lifespan in Japanese and European individuals (P_{heterogeneity} = 9.5 × 10^-8 for BMI). The causal effect of blood pressure and obesity on lifespan was further supported by Mendelian randomization studies. Beyond genotype-phenotype associations, our trans-biobank study offers a new value of PRSs in prioritization of risk factors that could be potential targets of medical treatment to improve population health.

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Comment in

Unraveling the genetic contributions to complex traits across different ethnic groups.
Mather KA, Thalamuthu A. Mather KA, et al. Nat Med. 2020 Apr;26(4):467-469. doi: 10.1038/s41591-020-0834-3. Nat Med. 2020. PMID: 32231296 No abstract available.

References

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Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan

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Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan

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