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Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study
- Source :
- Aging Cell, Aging Cell, Blackwell Publishing Ltd, 2013, 12 (2), pp.184-93. ⟨10.1111/acel.12039⟩, Beekman, M, Blanché, H, Perola, M, Hervonen, A, Bezrukov, V, Sikora, E, Flachsbart, F, Christiansen, L, De Craen, A J M, Kirkwood, T B L, Rea, I M, Poulain, M, Robine, J-M, Valensin, S, Stazi, M A, Passarino, G, Deiana, L, Gonos, E S, Paternoster, L, Sørensen, T, Tan, Q, Helmer, Q, van den Akker, E B, Deelen, J, Martella, F, Cordell, H J, Ayers, K L, Vaupel, J W, Törnwall, O, Johnson, T E, Schreiber, S, Lathrop, M, Skytthe, A, Westendorp, R G J, Christensen, K, Gampe, J, Nebel, A, Houwing-Duistermaat, J J, Slagboom, P E, Franceschi, C & GEHA consortium 2013, ' Genome-wide linkage analysis for human longevity : Genetics of Healthy Aging Study ', Aging Cell, vol. 12, no. 2, pp. 184-193 . https://doi.org/10.1111/acel.12039, Aging Cell; Vol 12, Beekman, M, Blanché, H, Perola, M, Hervonen, A, Bezrukov, V, Sikora, E, Flachsbart, F, Christiansen, L, De Craen, A J M, Kirkwood, T B L, Rea, I M, Poulain, M, Robine, J-M, Valensin, S, Stazi, M A, Passarino, G, Deiana, L, Gonos, E S, Paternoster, L, Sørensen, T I A, Tan, Q, Helmer, Q, Van den Akker, E B, Deelen, J, Martella, F, Cordell, H J, Ayers, K, Vaupel, J W, Törnwall, O, Johnson, T E, Schreiber, S, Lathrop, M, Skytthe, A, Westendorp, R G J, Christensen, K, Gampe, J, Nebel, A, Houwing-Duistermaat, J J, Slagboom, P E & Franceschi, C 2013, ' Genome-wide linkage analysis for human longevity: Genetics of healthy aging study ', Aging cell, vol. 12, no. 2, pp. 184-193 . https://doi.org/10.1111/acel.12039
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10 -8). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10 -5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.
- Subjects :
- Aging
Genetic Linkage
APOE gene
Genome-wide association study
Association analysis
Human familial longevity
[SHS]Humanities and Social Sciences
0302 clinical medicine
Mitochondrial Precursor Protein Import Complex Proteins
Cluster Analysis
Nonagenarian sibling pairs
media_common
Aged, 80 and over
Genetics
0303 health sciences
Longevity
Chromosome Mapping
Middle Aged
Europe
genome-wide linkage analysis
association analysis
nonagenarian sibling pairs
apoe gene
human familial longevity
congenital, hereditary, and neonatal diseases and abnormalities
media_common.quotation_subject
Locus (genetics)
Biology
Article
03 medical and health sciences
Apolipoproteins E
SDG 3 - Good Health and Well-being
Genetic linkage
Humans
Allele
Alleles
Aged
030304 developmental biology
Genetic association
Chromosomes, Human, Pair 14
Apolipoprotein C-I
Genome, Human
Siblings
Membrane Transport Proteins
Cell Biology
Heritability
Apoe gene
Genetic Loci
Human genome
Lod Score
Chromosomes, Human, Pair 19
Genome-wide linkage analysis
030217 neurology & neurosurgery
Chromosomes, Human, Pair 17
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 14749726
- Database :
- OpenAIRE
- Journal :
- Aging Cell, Aging Cell, Blackwell Publishing Ltd, 2013, 12 (2), pp.184-93. ⟨10.1111/acel.12039⟩, Beekman, M, Blanché, H, Perola, M, Hervonen, A, Bezrukov, V, Sikora, E, Flachsbart, F, Christiansen, L, De Craen, A J M, Kirkwood, T B L, Rea, I M, Poulain, M, Robine, J-M, Valensin, S, Stazi, M A, Passarino, G, Deiana, L, Gonos, E S, Paternoster, L, Sørensen, T, Tan, Q, Helmer, Q, van den Akker, E B, Deelen, J, Martella, F, Cordell, H J, Ayers, K L, Vaupel, J W, Törnwall, O, Johnson, T E, Schreiber, S, Lathrop, M, Skytthe, A, Westendorp, R G J, Christensen, K, Gampe, J, Nebel, A, Houwing-Duistermaat, J J, Slagboom, P E, Franceschi, C & GEHA consortium 2013, ' Genome-wide linkage analysis for human longevity : Genetics of Healthy Aging Study ', Aging Cell, vol. 12, no. 2, pp. 184-193 . https://doi.org/10.1111/acel.12039, Aging Cell; Vol 12, Beekman, M, Blanché, H, Perola, M, Hervonen, A, Bezrukov, V, Sikora, E, Flachsbart, F, Christiansen, L, De Craen, A J M, Kirkwood, T B L, Rea, I M, Poulain, M, Robine, J-M, Valensin, S, Stazi, M A, Passarino, G, Deiana, L, Gonos, E S, Paternoster, L, Sørensen, T I A, Tan, Q, Helmer, Q, Van den Akker, E B, Deelen, J, Martella, F, Cordell, H J, Ayers, K, Vaupel, J W, Törnwall, O, Johnson, T E, Schreiber, S, Lathrop, M, Skytthe, A, Westendorp, R G J, Christensen, K, Gampe, J, Nebel, A, Houwing-Duistermaat, J J, Slagboom, P E & Franceschi, C 2013, ' Genome-wide linkage analysis for human longevity: Genetics of healthy aging study ', Aging cell, vol. 12, no. 2, pp. 184-193 . https://doi.org/10.1111/acel.12039
- Accession number :
- edsair.doi.dedup.....68c6dfb2051f1b4efe281fb2a93d1179