Aladdin H Shadyab1, Charles Kooperberg2, Alexander P Reiner3, Sonia Jain4, JoAnn E Manson5,6, Chancellor Hohensee2, Caroline A Macera7, Richard A Shaffer7, Linda C Gallo8, Andrea Z LaCroix1. 1. Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine. 2. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. 3. Department of Epidemiology, University of Washington, Seattle. 4. Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine. 5. Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 7. Division of Epidemiology, Graduate School of Public Health, San Diego State University, California. 8. Department of Psychology, San Diego State University, California.
Abstract
BACKGROUND: No study has evaluated whether genetic factors are associated with longevity in African Americans or Hispanics, and it is unclear whether genetic factors are associated with healthy aging. METHODS: In this prospective study, we determined whether 14 genetic variants previously associated with longevity in genome-wide association studies were associated with survival to ages 85 and 90 in 11,053 postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. The associations of these variants with healthy aging, defined as survival to age 85 without chronic diseases or disability, were also determined. RESULTS: Among white women, three single nucleotide polymorphisms (SNPs) (rs2075650 [TOMM40], rs4420638 [APOC1], and rs429358 [APOE]) were significantly associated with survival to 90 years after correction for multiple testing (p < .001); rs4420638 and rs429358 were also significantly associated with healthy aging (p = .02). In African American women, no SNP was associated with longevity. In Hispanic women, 7 SNPs in linkage disequilibrium with a novel SNP, rs2149954, recently identified as being associated with increased longevity in a European population, were significantly associated with decreased survival to age 85 for carriers of the T versus C allele (p = .04). The association with decreased longevity was explained by higher risk of coronary heart disease in carriers of the T allele. There were no associations between FOXO3A SNPs and longevity in the analyses. In a meta-analysis, rs2075650 and rs429358 were significantly associated with longevity. CONCLUSIONS: Future studies are needed to identify novel loci associated with longevity in African American and Hispanic women to determine biologic pathways regulating life span in these groups.
BACKGROUND: No study has evaluated whether genetic factors are associated with longevity in African Americans or Hispanics, and it is unclear whether genetic factors are associated with healthy aging. METHODS: In this prospective study, we determined whether 14 genetic variants previously associated with longevity in genome-wide association studies were associated with survival to ages 85 and 90 in 11,053 postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. The associations of these variants with healthy aging, defined as survival to age 85 without chronic diseases or disability, were also determined. RESULTS: Among white women, three single nucleotide polymorphisms (SNPs) (rs2075650 [TOMM40], rs4420638 [APOC1], and rs429358 [APOE]) were significantly associated with survival to 90 years after correction for multiple testing (p < .001); rs4420638 and rs429358 were also significantly associated with healthy aging (p = .02). In African American women, no SNP was associated with longevity. In Hispanic women, 7 SNPs in linkage disequilibrium with a novel SNP, rs2149954, recently identified as being associated with increased longevity in a European population, were significantly associated with decreased survival to age 85 for carriers of the T versus C allele (p = .04). The association with decreased longevity was explained by higher risk of coronary heart disease in carriers of the T allele. There were no associations between FOXO3A SNPs and longevity in the analyses. In a meta-analysis, rs2075650 and rs429358 were significantly associated with longevity. CONCLUSIONS: Future studies are needed to identify novel loci associated with longevity in African American and Hispanic women to determine biologic pathways regulating life span in these groups.
Authors: Thomas J Hoffmann; Stephen K Van Den Eeden; Lori C Sakoda; Eric Jorgenson; Laurel A Habel; Rebecca E Graff; Michael N Passarelli; Clinton L Cario; Nima C Emami; Chun R Chao; Nirupa R Ghai; Jun Shan; Dilrini K Ranatunga; Charles P Quesenberry; David Aaronson; Joseph Presti; Zhaoming Wang; Sonja I Berndt; Stephen J Chanock; Shannon K McDonnell; Amy J French; Daniel J Schaid; Stephen N Thibodeau; Qiyuan Li; Matthew L Freedman; Kathryn L Penney; Lorelei A Mucci; Christopher A Haiman; Brian E Henderson; Daniela Seminara; Mark N Kvale; Pui-Yan Kwok; Catherine Schaefer; Neil Risch; John S Witte Journal: Cancer Discov Date: 2015-06-01 Impact factor: 39.397
Authors: Linda Broer; Aron S Buchman; Joris Deelen; Daniel S Evans; Jessica D Faul; Kathryn L Lunetta; Paola Sebastiani; Jennifer A Smith; Albert V Smith; Toshiko Tanaka; Lei Yu; Alice M Arnold; Thor Aspelund; Emelia J Benjamin; Philip L De Jager; Gudny Eirkisdottir; Denis A Evans; Melissa E Garcia; Albert Hofman; Robert C Kaplan; Sharon L R Kardia; Douglas P Kiel; Ben A Oostra; Eric S Orwoll; Neeta Parimi; Bruce M Psaty; Fernando Rivadeneira; Jerome I Rotter; Sudha Seshadri; Andrew Singleton; Henning Tiemeier; André G Uitterlinden; Wei Zhao; Stefania Bandinelli; David A Bennett; Luigi Ferrucci; Vilmundur Gudnason; Tamara B Harris; David Karasik; Lenore J Launer; Thomas T Perls; P Eline Slagboom; Gregory J Tranah; David R Weir; Anne B Newman; Cornelia M van Duijn; Joanne M Murabito Journal: J Gerontol A Biol Sci Med Sci Date: 2014-09-08 Impact factor: 6.053
Authors: Bradley J Willcox; Timothy A Donlon; Qimei He; Randi Chen; John S Grove; Katsuhiko Yano; Kamal H Masaki; D Craig Willcox; Beatriz Rodriguez; J David Curb Journal: Proc Natl Acad Sci U S A Date: 2008-09-02 Impact factor: 11.205
Authors: Timothy A Donlon; Brian J Morris; Qimei He; Randi Chen; Kamal H Masaki; Richard C Allsopp; D Craig Willcox; Gregory J Tranah; Neeta Parimi; Daniel S Evans; Friederike Flachsbart; Almut Nebel; Duk-Hwan Kim; Joobae Park; Bradley J Willcox Journal: J Gerontol A Biol Sci Med Sci Date: 2017-08-01 Impact factor: 6.053
Authors: Aladdin H Shadyab; JoAnn E Manson; Wenjun Li; Margery Gass; Robert L Brunner; Michelle J Naughton; Brad Cannell; Barbara V Howard; Andrea Z LaCroix Journal: Age Ageing Date: 2018-11-01 Impact factor: 10.668
Authors: Anatoliy I Yashin; Konstantin G Arbeev; Deqing Wu; Liubov S Arbeeva; Olivia Bagley; Eric Stallard; Alexander M Kulminski; Igor Akushevich; Fang Fang; Mary K Wojczynski; Kaare Christensen; Anne B Newman; Robert M Boudreau; Michael A Province; Stephen Thielke; Thomas T Perls; Ping An; Irma Elo; Svetlana V Ukraintseva Journal: J Gerontol A Biol Sci Med Sci Date: 2018-10-08 Impact factor: 6.053
Authors: Selma M Soyal; Markus Kwik; Ognian Kalev; Stefan Lenz; Greta Zara; Peter Strasser; Wolfgang Patsch; Serge Weis Journal: Mol Genet Genomic Med Date: 2020-05-30 Impact factor: 2.183
Authors: Joris Deelen; Daniel S Evans; Dan E Arking; Niccolò Tesi; Marianne Nygaard; Xiaomin Liu; Mary K Wojczynski; Mary L Biggs; Ashley van der Spek; Gil Atzmon; Erin B Ware; Chloé Sarnowski; Albert V Smith; Ilkka Seppälä; Heather J Cordell; Janina Dose; Najaf Amin; Alice M Arnold; Kristin L Ayers; Nir Barzilai; Elizabeth J Becker; Marian Beekman; Hélène Blanché; Kaare Christensen; Lene Christiansen; Joanna C Collerton; Sarah Cubaynes; Steven R Cummings; Karen Davies; Birgit Debrabant; Jean-François Deleuze; Rachel Duncan; Jessica D Faul; Claudio Franceschi; Pilar Galan; Vilmundur Gudnason; Tamara B Harris; Martijn Huisman; Mikko A Hurme; Carol Jagger; Iris Jansen; Marja Jylhä; Mika Kähönen; David Karasik; Sharon L R Kardia; Andrew Kingston; Thomas B L Kirkwood; Lenore J Launer; Terho Lehtimäki; Wolfgang Lieb; Leo-Pekka Lyytikäinen; Carmen Martin-Ruiz; Junxia Min; Almut Nebel; Anne B Newman; Chao Nie; Ellen A Nohr; Eric S Orwoll; Thomas T Perls; Michael A Province; Bruce M Psaty; Olli T Raitakari; Marcel J T Reinders; Jean-Marie Robine; Jerome I Rotter; Paola Sebastiani; Jennifer Smith; Thorkild I A Sørensen; Kent D Taylor; André G Uitterlinden; Wiesje van der Flier; Sven J van der Lee; Cornelia M van Duijn; Diana van Heemst; James W Vaupel; David Weir; Kenny Ye; Yi Zeng; Wanlin Zheng; Henne Holstege; Douglas P Kiel; Kathryn L Lunetta; P Eline Slagboom; Joanne M Murabito Journal: Nat Commun Date: 2019-08-14 Impact factor: 14.919
Authors: Anna Zettergren; Silke Kern; Lina Rydén; Svante Östling; Kaj Blennow; Henrik Zetterberg; Hanna Falk; Ingmar Skoog Journal: J Gerontol A Biol Sci Med Sci Date: 2018-10-08 Impact factor: 6.053