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Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging.
Timmers, Paul R H J; Tiys, Evgeny S; Sakaue, Saori; Akiyama, Masato; Kiiskinen, Tuomo T J; Zhou, Wei; Hwang, Shih-Jen; Yao, Chen; Deelen, Joris; Levy, Daniel; Ganna, Andrea; Kamatani, Yoichiro; Okada, Yukinori; Joshi, Peter K; Wilson, James F; Tsepilov, Yakov A.
  • Timmers PRHJ; MRC Human Genetics Unit, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. paul.timmers@ed.ac.uk.
  • Tiys ES; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK. paul.timmers@ed.ac.uk.
  • Sakaue S; Laboratory of Theoretical and Applied Functional Genomics, Novosibirsk State University, Novosibirsk, Russia.
  • Akiyama M; Laboratory of Glycogenomics, Institute of Cytology and Genetics, Novosibirsk, Russia.
  • Kiiskinen TTJ; Center for Data Sciences, Harvard Medical School, Boston, MA, USA.
  • Zhou W; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Hwang SJ; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Yao C; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Deelen J; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Levy D; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Ganna A; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Kamatani Y; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Okada Y; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Joshi PK; Framingham Heart Study, Framingham, MA, USA.
  • Wilson JF; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Tsepilov YA; Framingham Heart Study, Framingham, MA, USA.
Nat Aging ; 2(1): 19-30, 2022 01.
Artículo en Inglés | MEDLINE | ID: covidwho-2319893
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.
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Estudio de Asociación del Genoma Completo / Análisis de la Aleatorización Mendeliana Tipo de estudio: Estudio experimental / Estudio pronóstico Límite: Femenino / Humanos Idioma: Inglés Revista: Nat Aging Año: 2022 Tipo del documento: Artículo País de afiliación: S43587-021-00159-8

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Estudio de Asociación del Genoma Completo / Análisis de la Aleatorización Mendeliana Tipo de estudio: Estudio experimental / Estudio pronóstico Límite: Femenino / Humanos Idioma: Inglés Revista: Nat Aging Año: 2022 Tipo del documento: Artículo País de afiliación: S43587-021-00159-8