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J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1453-1464. doi: 10.1093/gerona/glx027.

Four Genome-Wide Association Studies Identify New Extreme Longevity Variants.

Author information

1
Department of Biostatistics, Boston University School of Public Health, Massachusetts.
2
Bioinformatics Program, Boston University, Massachusetts.
3
College of Public Health and Human Sciences, Oregon State University, Corvallis.
4
Geriatrics Section, Department of Medicine, Boston University School of Medicine & Boston Medical Center, Massachusetts.
5
Laboratory of Informatics and Systems Engineering for Clinical Research, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy.
6
Department of Natural Science, University of Haifa, Israel.
7
Department of Medicine.
8
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York.
9
IRCCS MultiMedica, Milan, Italy.
10
Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
11
Division of Statistical Genomics, Washington University School of Medicine, Saint Louis, Missouri.

Abstract

The search for the genetic determinants of extreme human longevity has been challenged by the phenotype's rarity and its nonspecific definition by investigators. To address these issues, we established a consortium of four studies of extreme longevity that contributed 2,070 individuals who survived to the oldest one percentile of survival for the 1900 U.S. birth year cohort. We conducted various analyses to discover longevity-associated variants (LAV) and characterized those LAVs that differentiate survival to extreme age at death (eSAVs) from those LAVs that become more frequent in centenarians because of mortality selection (eg, survival to younger years). The analyses identified new rare variants in chromosomes 4 and 7 associated with extreme survival and with reduced risk for cardiovascular disease and Alzheimer's disease. The results confirm the importance of studying truly rare survival to discover those combinations of common and rare variants associated with extreme longevity and longer health span.

KEYWORDS:

Genetic profiles; Genetic variants; Healthy aging; Human longevity

PMID:
28329165
PMCID:
PMC5861867
[Available on 2018-10-12]
DOI:
10.1093/gerona/glx027
[Indexed for MEDLINE]

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