Sex Differences in Genetic Associations With Longevity
Y Zeng
(1, 2)
,
C Nie
(3)
,
J Min
(4)
,
H Chen
(1, 5)
,
X Liu
(3)
,
R Ye
(3)
,
Z Chen
(3)
,
C Bai
(2)
,
E Xie
(4)
,
Z Yin
(6)
,
Y Lv
(6)
,
J Lu
(2)
,
J Li
(2)
,
T Ni
(7)
,
L Bolund
(3, 8)
,
Kc Land
(1)
,
A Yashin
(1)
,
Am O’rand
(1)
,
L Sun
(9)
,
Z Yang
(9)
,
W Tao
(2)
,
A Gurinovich
(10)
,
C Franceschi
(11)
,
J Xie
(1)
,
J Gu
(2)
,
Y Hou
(3)
,
X Xu
(3)
,
Jean-Marie Robine
(12, 13, 14)
,
J Deelen
(15)
,
P Sebastiani
(10)
,
E Slagboom
(16)
,
T Perls
(10)
,
E Hauser
(1)
,
W Gottschalk
(1)
,
Q Tan
(17)
,
K Christensen
(17)
,
X Shi
(6)
,
M Lutz
(1)
,
X-L Tian
(18)
,
H Yang
(3, 19)
,
J Vaupel
(20)
1
Duke University [Durham]
2 Peking University [Beijing]
3 UCAS - University of Chinese Academy of Sciences [Beijing]
4 Zhejiang University
5 Xiangtan University
6 Chinese Center for Disease Control and Prevention
7 Fudan University [Shanghai]
8 Aarhus University [Aarhus]
9 Beijing Tongren Hospital
10 BU - Boston University [Boston]
11 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
12 CERMES3 - UMR 8211 / U988 / UM 7 - CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société
13 EPHE - École Pratique des Hautes Études
14 UM - Université de Montpellier
15 Max planck Institute for Biology of Ageing [Cologne]
16 LUMC - Leiden University Medical Center
17 SDU - University of Southern Denmark
18 Nanchang University
19 James D. Watson Institute of Genome Sciences
20 MPIDR - Max Planck Institute for Demographic Research
2 Peking University [Beijing]
3 UCAS - University of Chinese Academy of Sciences [Beijing]
4 Zhejiang University
5 Xiangtan University
6 Chinese Center for Disease Control and Prevention
7 Fudan University [Shanghai]
8 Aarhus University [Aarhus]
9 Beijing Tongren Hospital
10 BU - Boston University [Boston]
11 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
12 CERMES3 - UMR 8211 / U988 / UM 7 - CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société
13 EPHE - École Pratique des Hautes Études
14 UM - Université de Montpellier
15 Max planck Institute for Biology of Ageing [Cologne]
16 LUMC - Leiden University Medical Center
17 SDU - University of Southern Denmark
18 Nanchang University
19 James D. Watson Institute of Genome Sciences
20 MPIDR - Max Planck Institute for Demographic Research
Jean-Marie Robine
- Fonction : Auteur
- PersonId : 746403
- IdHAL : jm-robine
- ORCID : 0000-0002-4111-6195
- IdRef : 031816533
Résumé
Importance: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care.
Objective: To explore sex differences in genetic associations with longevity.
Design setting and participants: This population-based case-control study used sex-specific genome-wide association study and polygenic risk score (PRS) analyses to examine sex differences in genetic associations with longevity. Five hundred sixty-four male and 1614 female participants older than 100 years were compared with a control group of 773 male and 1526 female individuals aged 40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study participants with Han ethnicity who were recruited in 1998 and 2008 to 2014.
Main outcomes and measures: Sex-specific loci and pathways associated with longevity and PRS measures of joint effects of sex-specific loci.
Results: Eleven male-specific and 11 female-specific longevity loci (P < 10-5) and 35 male-specific and 25 female-specific longevity loci (10-5 ≤ P < 10-4) were identified. Each of these loci's associations with longevity were replicated in north and south regions of China in one sex but were not significant in the other sex (P = .13-.97), and loci-sex interaction effects were significant (P < .05). The associations of loci rs60210535 of the LINC00871 gene with longevity were replicated in Chinese women (P = 9.0 × 10-5) and US women (P = 4.6 × 10-5) but not significant in Chinese and US men. The associations of the loci rs2622624 of the ABCG2 gene were replicated in Chinese women (P = 6.8 × 10-5) and European women (P = .003) but not significant in both Chinese and European men. Eleven male-specific pathways (inflammation and immunity genes) and 34 female-specific pathways (tryptophan metabolism and PGC-1α induced) were significantly associated with longevity (P < .005; false discovery rate < 0.05). The PRS analyses demonstrated that sex-specific associations with longevity of the 4 exclusive groups of 11 male-specific and 11 female-specific loci (P < 10-5) and 35 male-specific and 25 female-specific loci (10-5 ≤P < 10-4) were jointly replicated across north and south discovery and target samples. Analyses using the combined data set of north and south showed that these 4 groups of sex-specific loci were jointly and significantly associated with longevity in one sex (P = 2.9 × 10-70 to 1.3 × 10-39) but not jointly significant in the other sex (P = .11 to .70), while interaction effects between PRS and sex were significant (P = 4.8 × 10-50 to 1.2 × 10-16).
Conclusion and relevance: The sex differences in genetic associations with longevity are remarkable, but have been overlooked by previously published genome-wide association studies on longevity. This study contributes to filling this research gap and provides a scientific basis for further investigating effects of sex-specific genetic variants and their interactions with environment on healthy aging, which may substantially contribute to more effective and targeted individualized health care for male and female elderly individuals.
Domaines
Sciences de l'Homme et SociétéFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Sex Differences in Genetic Associations With Longevity
|
Résumé |
en
Importance: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care.
Objective: To explore sex differences in genetic associations with longevity.
Design setting and participants: This population-based case-control study used sex-specific genome-wide association study and polygenic risk score (PRS) analyses to examine sex differences in genetic associations with longevity. Five hundred sixty-four male and 1614 female participants older than 100 years were compared with a control group of 773 male and 1526 female individuals aged 40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study participants with Han ethnicity who were recruited in 1998 and 2008 to 2014.
Main outcomes and measures: Sex-specific loci and pathways associated with longevity and PRS measures of joint effects of sex-specific loci.
Results: Eleven male-specific and 11 female-specific longevity loci (P < 10-5) and 35 male-specific and 25 female-specific longevity loci (10-5 ≤ P < 10-4) were identified. Each of these loci's associations with longevity were replicated in north and south regions of China in one sex but were not significant in the other sex (P = .13-.97), and loci-sex interaction effects were significant (P < .05). The associations of loci rs60210535 of the LINC00871 gene with longevity were replicated in Chinese women (P = 9.0 × 10-5) and US women (P = 4.6 × 10-5) but not significant in Chinese and US men. The associations of the loci rs2622624 of the ABCG2 gene were replicated in Chinese women (P = 6.8 × 10-5) and European women (P = .003) but not significant in both Chinese and European men. Eleven male-specific pathways (inflammation and immunity genes) and 34 female-specific pathways (tryptophan metabolism and PGC-1α induced) were significantly associated with longevity (P < .005; false discovery rate < 0.05). The PRS analyses demonstrated that sex-specific associations with longevity of the 4 exclusive groups of 11 male-specific and 11 female-specific loci (P < 10-5) and 35 male-specific and 25 female-specific loci (10-5 ≤P < 10-4) were jointly replicated across north and south discovery and target samples. Analyses using the combined data set of north and south showed that these 4 groups of sex-specific loci were jointly and significantly associated with longevity in one sex (P = 2.9 × 10-70 to 1.3 × 10-39) but not jointly significant in the other sex (P = .11 to .70), while interaction effects between PRS and sex were significant (P = 4.8 × 10-50 to 1.2 × 10-16).
Conclusion and relevance: The sex differences in genetic associations with longevity are remarkable, but have been overlooked by previously published genome-wide association studies on longevity. This study contributes to filling this research gap and provides a scientific basis for further investigating effects of sex-specific genetic variants and their interactions with environment on healthy aging, which may substantially contribute to more effective and targeted individualized health care for male and female elderly individuals.
|
Auteur(s) |
Y Zeng
1, 2
, C Nie
3
, J Min
4
, H Chen
1, 5
, X Liu
3
, R Ye
3
, Z Chen
3
, C Bai
2
, E Xie
4
, Z Yin
6
, Y Lv
6
, J Lu
2
, J Li
2
, T Ni
7
, L Bolund
3, 8
, Kc Land
1
, A Yashin
1
, Am O’rand
1
, L Sun
9
, Z Yang
9
, W Tao
2
, A Gurinovich
10
, C Franceschi
11
, J Xie
1
, J Gu
2
, Y Hou
3
, X Xu
3
, Jean-Marie Robine
12, 13, 14
, J Deelen
15
, P Sebastiani
10
, E Slagboom
16
, T Perls
10
, E Hauser
1
, W Gottschalk
1
, Q Tan
17
, K Christensen
17
, X Shi
6
, M Lutz
1
, X-L Tian
18
, H Yang
3, 19
, J Vaupel
20
1
Duke University [Durham]
( 95351 )
- Durham, NC 27708
- États-Unis
2
Peking University [Beijing]
( 300884 )
- No.5 Yiheyuan Road Haidian District, Beijing, P.R.China 100871
- Chine
3
UCAS -
University of Chinese Academy of Sciences [Beijing]
( 469160 )
- No.19(A) Yuquan Road, Shijingshan District, Beijing, P.R.China 100049
- Chine
4
Zhejiang University
( 8138 )
- 866 Yuhangtang Road * Hangzhou * Zhejiang Province * 310058 * P. R. China
- Chine
5
Xiangtan University
( 469145 )
- Xiangtan City Hunan 411105 China
- Chine
6
Chinese Center for Disease Control and Prevention
( 222141 )
- 155 Changbai Road Changping District ,Beijing 102206,China
- Chine
7
Fudan University [Shanghai]
( 140179 )
- Shanghai, Yangpu
- Chine
8
Aarhus University [Aarhus]
( 19908 )
- Nordre Ringgade 1 DK-8000 Aarhus C
- Danemark
9
Beijing Tongren Hospital
( 458561 )
- Beijing, Chine
- Chine
10
BU -
Boston University [Boston]
( 63395 )
- One Silber Way, Boston, MA 02215
- États-Unis
11
UNIBO -
Alma Mater Studiorum Università di Bologna = University of Bologna
( 30978 )
- Via Zamboni, 33 - 40126 Bologna
- Italie
12
CERMES3 - UMR 8211 / U988 / UM 7 -
CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société
( 176631 )
- 7 rue Guy Môquet - BP 8 - 94801 Villejuif Cedex
Site administratif : Campus CNRS- 7, rue Guy Môquet- BP 8- 94801 Villejuif Cedex
Site Paris: CUSP (Centre universitaire des Saints-Pères)- Bâtiment Jacob (3ème étage)- 45, rue des Saints-Pères- 75270 Paris Cedex 06
- France
13
EPHE -
École Pratique des Hautes Études
( 110691 )
- 4-14 Rue Ferrus, 75014 Paris
- France
14
UM -
Université de Montpellier
( 410122 )
- 163 rue Auguste Broussonnet - 34090 Montpellier
- France
15
Max planck Institute for Biology of Ageing [Cologne]
( 519492 )
- Joseph-Stelzmann-Str. 9b
D-50931 Cologne
- Allemagne
16
LUMC -
Leiden University Medical Center
( 300851 )
- Leids Universitair Medisch Centrum, Universiteit Leiden - 1233 ZA, Leiden
- Pays-Bas
17
SDU -
University of Southern Denmark
( 50786 )
- 5320 Odense
- Danemark
18
Nanchang University
( 463362 )
- Nanchang Jiangxi 330031 China
- Chine
19
James D. Watson Institute of Genome Sciences
( 1036461 )
- Chine
20
MPIDR -
Max Planck Institute for Demographic Research
( 114184 )
- Konrad-Zuse-Straße 1, 18057 Rostock
- Allemagne
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2018
|
Volume |
1
|
Numéro |
4
|
Page/Identifiant |
e181670
|
Domaine(s) |
|
DOI | 10.1001/jamanetworkopen.2018.1670 |
Pubmed Id | 30294719 |
PubMed Central | PMC6173523 |
Origine :
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