Genome-wide association study identifies a single major locus contributing to 
survival into old age; the APOE locus revisited

Deelen, J.; Beekman, M.; Uh, H. W.; Helmer, Q.; Kuningas, M.; Christiansen, L.; Kremer, D.; van der Breggen, R.; Suchiman, H. E.; Lakenberg, N.; van den Akker, E. B.; Passtoors, W. M.; Tiemeier, H.; van Heemst, D.; de Craen, A. J.; Rivadeneira, F.; de Geus, E. J.; Perola, M.; van der Ouderaa, F. J.; Gunn, D. A.; Boomsma, D. I.; Uitterlinden, A. G.; Christensen, K.; van Duijn, C. M.; Heijmans, B. T.; Houwing-Duistermaat, J. J.; Westendorp, R. G.; Slagboom, P. E.

doi:10.1111/j.1474-9726.2011.00705.x

Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

Deelen, J., Beekman, M., Uh, H. W., Helmer, Q., Kuningas, M., Christiansen, L., Kremer, D., van der Breggen, R., Suchiman, H. E., Lakenberg, N., van den Akker, E. B., Passtoors, W. M., Tiemeier, H., van Heemst, D., de Craen, A. J., Rivadeneira, F., de Geus, E. J., Perola, M., van der Ouderaa, F. J., Gunn, D. A., Boomsma, D. I., Uitterlinden, A. G., Christensen, K., van Duijn, C. M., Heijmans, B. T., Houwing-Duistermaat, J. J., Westendorp, R. G., & Slagboom, P. E. (2011). Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell, 10(4), 686-98. doi:10.1111/j.1474-9726.2011.00705.x.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-000B-A35D-5 版のパーマリンク: https://hdl.handle.net/21.11116/0000-000C-08A1-5

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Deelen, J.¹, 著者
Beekman, M., 著者
Uh, H. W., 著者
Helmer, Q., 著者
Kuningas, M., 著者
Christiansen, L., 著者
Kremer, D., 著者
van der Breggen, R., 著者
Suchiman, H. E., 著者
Lakenberg, N., 著者
van den Akker, E. B., 著者
Passtoors, W. M., 著者
Tiemeier, H., 著者
van Heemst, D., 著者
de Craen, A. J., 著者
Rivadeneira, F., 著者
de Geus, E. J., 著者
Perola, M., 著者
van der Ouderaa, F. J., 著者
Gunn, D. A., 著者
Boomsma, D. I., 著者Uitterlinden, A. G., 著者Christensen, K., 著者van Duijn, C. M., 著者Heijmans, B. T., 著者Houwing-Duistermaat, J. J., 著者Westendorp, R. G., 著者Slagboom, P. E., 著者全て表示

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1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006

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キーワード: Adult Aged Aged, 80 and over Alzheimer Disease/genetics Apolipoproteins E/*genetics Case-Control Studies Cohort Studies Female Forkhead Box Protein O3 Forkhead Transcription Factors/genetics Genetic Loci Genetic Predisposition to Disease *Genome, Human Genome-Wide Association Study Humans Linkage Disequilibrium Longevity/*genetics Longitudinal Studies Male Middle Aged Polymorphism, Single Nucleotide Proto-Oncogene Proteins c-akt/genetics

要旨: By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P<1x10(-4) ) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR=0.71 (95% CI 0.65-0.77), P=3.39 x 10(-17) ]. This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE epsilon4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P=0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE epsilon4 allele. No other major longevity locus was found.

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日付: オンライン出版: 2011-08出版: 2011-03-23

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識別子（DOI, ISBNなど）: その他: 21418511
DOI: 10.1111/j.1474-9726.2011.00705.x
ISSN: 1474-9726 (Electronic)1474-9718 (Linking)

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出版物名: Aging Cell

種別: 学術雑誌

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ページ: - 巻号: 10 (4) 通巻号: - 開始・終了ページ: 686 - 98 識別子（ISBN, ISSN, DOIなど）: -

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