Four Genome-Wide Association Studies Identify New Extreme Longevity Variants

被引：75

作者：

Sebastiani, Paola ^{[1
]}

Gurinovich, Anastasia ^{[2
]}

Bae, Harold ^{[3
]}

Andersen, Stacy ^{[4
,5
]}

Malovini, Alberto ^{[6
]}

Atzmon, Gil ^{[7
,8
,9
]}

Villa, Francesco ^{[10
,11
]}

Kraja, Aldi T. ^{[12
]}

Ben-Avraham, Danny ^{[8
,9
]}

Barzilai, Nir ^{[8
,9
]}

Puca, Annibale ^{[10
,11
]}

Perls, Thomas T. ^{[4
,5
]}

机构：

[1] Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave, Boston, MA 02118 USA

[2] Boston Univ, Bioinformat Program, Boston, MA 02215 USA

[3] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA

[4] Boston Univ, Sch Med, Dept Med, Geriatr Sect, Boston, MA 02118 USA

[5] Boston Med Ctr, Boston, MA USA

[6] IRCCS Fdn Salvatore Maugeri, Lab Informat & Syst Engn Clin Res, Pavia, Italy

[7] Univ Haifa, Dept Nat Sci, Haifa, Israel

[8] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA

[9] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA

[10] IRCCS MultiMed, Milan, Italy

[11] Univ Salerno, Dept Med & Surg, Baronissi, Italy

[12] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA

来源：

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2017年 / 72卷 / 11期

关键词：

Genetic variants; Human longevity; Healthy aging; Genetic profiles; FATTY-ACID PROFILE; DISEASE VARIANTS; CONFIRMS APOE; LIFE-SPAN; METAANALYSIS; SURVIVAL; LOCUS; RISK; AGE; CENTENARIANS;

D O I：

10.1093/gerona/glx027

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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.

引用

页码：1453 / 1464

页数：12

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