Universität zu Köln

Timmers, Paul R. H. J., Tiys, Evgeny S., Sakaue, Saori ORCID: 0000-0003-3618-9717, Akiyama, Masato ORCID: 0000-0002-1879-5476, Kiiskinen, Tuomo T. J., Zhou, Wei, Hwang, Shih-Jen, Yao, Chen, Deelen, Joris, Levy, Daniel, Ganna, Andrea ORCID: 0000-0002-8147-240X, Kamatani, Yoichiro, Okada, Yukinori, Joshi, Peter K. K., Wilson, James F. F. and Tsepilov, Yakov A. A. (2022). Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging. Nature Aging, 2 (1). S. 19 - 36. LONDON: SPRINGERNATURE. ISSN 2662-8465

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Abstract

Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits-healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health-in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near HTT and MAML3 using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging. Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Timmers, Paul R. H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tiys, Evgeny S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sakaue, Saori UNSPECIFIED orcid.org/0000-0003-3618-9717 UNSPECIFIED Akiyama, Masato UNSPECIFIED orcid.org/0000-0002-1879-5476 UNSPECIFIED Kiiskinen, Tuomo T. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Wei UNSPECIFIED UNSPECIFIED UNSPECIFIED Hwang, Shih-Jen UNSPECIFIED UNSPECIFIED UNSPECIFIED Yao, Chen UNSPECIFIED UNSPECIFIED UNSPECIFIED Deelen, Joris UNSPECIFIED UNSPECIFIED UNSPECIFIED Levy, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Ganna, Andrea UNSPECIFIED orcid.org/0000-0002-8147-240X UNSPECIFIED Kamatani, Yoichiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Okada, Yukinori UNSPECIFIED UNSPECIFIED UNSPECIFIED Joshi, Peter K. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilson, James F. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsepilov, Yakov A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-695561
DOI:	10.1038/s43587-021-00159-8
Journal or Publication Title:	Nature Aging
Volume:	2
Number:	1
Page Range:	S. 19 - 36
Date:	2022
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	2662-8465
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; RISK-FACTOR; LIPOPROTEIN(A); BRAIN; HERITABILITY; DATABASE; BLOOD; LRP12 Multiple languages Cell Biology; Geriatrics & Gerontology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69556