27 results on '"Christiansen, Lene"'
Search Results
2. Exome-Wide Association Study Identifies FN3KRP and PGP as New Candidate Longevity Genes.
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Torres, Guillermo G., Nygaard, Marianne, Caliebe, Amke, Blanché, Hélène, Chantalat, Sophie, Galan, Pilar, Lieb, Wolfgang, Christiansen, Lene, Deleuze, Jean-François, Christensen, Kaare, Strauch, Konstantin, Müller-Nurasyid, Martina, Peters, Annette, Nöthen, Markus M., Hoffmann, Per, Flachsbart, Friederike, Schreiber, Stefan, Ellinghaus, David, Franke, Andre, and Dose, Janina
- Abstract
Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62 488 common and rare coding variants in 1248 German long-lived individuals, including 599 centenarians and 6941 younger controls (age < 60 years). In a single-variant analysis, we observed an exome-wide significant association between rs1046896 in the gene fructosamine-3-kinase-related-protein (FN3KRP) and longevity. Noteworthy, we found the longevity allele C of rs1046896 to be associated with an increased FN3KRP expression in whole blood; a database look-up confirmed this effect for various other human tissues. A gene-based analysis, in which potential cumulative effects of common and rare variants were considered, yielded the gene phosphoglycolate phosphatase (PGP) as another potential longevity gene, though no single variant in PGP reached the discovery p-value (1 × 10E−04). Furthermore, we validated the previously reported longevity locus cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1). Replication of our results in a French longevity cohort was only successful for rs1063192 in CDKN2B AS1. In conclusion, we identified 2 new potential candidate longevity genes, FN3KRP and PGP which may influence the phenotype through their role in metabolic processes, that is, the reverse glycation of proteins (FN3KRP) and the control of glycerol-3-phosphate levels (PGP). [ABSTRACT FROM AUTHOR]
- Published
- 2021
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3. Cohort Differences in the Associations of Selected Candidate Genes With Risk of All-Cause Mortality at Advanced Ages.
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Tan, Qihua, Jacobsen, Rune, Nygaard, Marianne, Soerensen, Mette, Mengel-From, Jonas, Christiansen, Lene, and Christensen, Kaare
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AGING ,ALLELES ,APOLIPOPROTEINS ,CONFIDENCE intervals ,GENES ,GENETIC polymorphisms ,LONGEVITY ,LONGITUDINAL method ,MEMBRANE proteins ,MORTALITY ,RISK assessment ,SURVIVAL analysis (Biometry) ,RELATIVE medical risk ,DESCRIPTIVE statistics - Abstract
Considerable efforts have been made to identify the genetic basis of human longevity, with only limited progress. One important drawback of current genetic studies is the limited knowledge of gene-environment interaction. Using 2 cohorts of long-lived individuals born in 1905 and 1915 in Denmark, we performed survival analysis to estimate risk of mortality for major candidate genes of aging and longevity and their cohort effects. Through statistical modeling that combines individual genetic and survival information with cohort-specific survival data, we estimated the relative risks of mortality from ages 95 to 103 years associated with genetic variants in apolipoprotein E (APOE) , forkhead box class O3a , clusterin, and phosphatidylinositol binding clathrin assembly protein. Our analysis estimated a decreased risk of carrying the APOE |$\varepsilon $| 4 allele (change in risk = –0.403, 95% confidence interval (CI): −0.831, 0.021; P = 0.040) in men of the later cohort, although the allele itself was harmful to survival across sexes (relative risk = 1.161, 95% CI: 1.027, 1.345; P = 0.026). We also estimated a cohort effect of increased risk for the minor allele of rs3851179 in phosphatidylinositol binding clathrin assembly protein with borderline significance (change in risk = 0.165, 95% CI: −0.010, 0.331; P = 0.052) in women. Our estimated significant cohort effect on APOE |$\varepsilon $| 4 is indicative of the interplay between the gene and the changing environment that modulates survival at extreme ages. [ABSTRACT FROM AUTHOR]
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- 2020
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4. Advanced Parental Age at Conception and Sex Affects Mitochondrial DNA Copy Number in Human and Fruit Flies.
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Mengel-From, Jonas, Svane, Anne Marie, Pertoldi, Cino, Kristensen, Torsten Nygaard, Loeschcke, Volker, Skytthe, Axel, Christensen, Kaare, Lindahl-Jacobsen, Rune, Hjelmborg, Jacob, Christiansen, Lene, and Nygaard Kristensen, Torsten
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MITOCHONDRIAL DNA ,FRUIT flies ,MATERNAL age ,CONCEPTION ,DROSOPHILA melanogaster - Abstract
Aging is a multifactorial trait caused by early as well as late-life circumstances. A society trend that parents deliberately delay having children is of concern to health professionals, for example as advanced parental age at conception increases disease risk profiles in offspring. We here aim to study if advanced parental age at conception affects mitochondrial DNA content, a cross-species biomarker of general health, in adult human twin offspring and in a model organism. We find no deteriorated mitochondrial DNA content at advanced parental age at conception, but human mitochondrial DNA content was higher in females than males, and the difference was twofold higher at advanced maternal age at conception. Similar parental age effects and sex-specific differences in mitochondrial DNA content were found in Drosophila melanogaster. In addition, parental longevity in humans associates with both mitochondrial DNA content and parental age at conception; thus, we carefully propose that a poorer disease risk profile from advanced parental age at conception might be surpassed by superior effects of parental successful late-life reproduction that associate with parental longevity. [ABSTRACT FROM AUTHOR]
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- 2019
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5. APOE Alleles and Extreme Human Longevity.
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Sebastiani, Paola, Gurinovich, Anastasia, Nygaard, Marianne, Sasaki, Takashi, Sweigart, Benjamin, Bae, Harold, Andersen, Stacy L, Villa, Francesco, Atzmon, Gil, Christensen, Kaare, Arai, Yasumichi, Barzilai, Nir, Puca, Annibale, Christiansen, Lene, Hirose, Nobuyoshi, and Perls, Thomas T
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LONGEVITY ,APOLIPOPROTEIN E ,ALLELES ,CENTENARIANS ,AGING - Abstract
We assembled a collection of 28,297 participants from seven studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity, and the Health and Retirement Studies to investigate the association between the APOE alleles ε2ε3 and ε4 and extreme human longevity and age at death. By using three different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ε4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ε2ε2 or ε2ε3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared with carrying the genotype ε3ε3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population. [ABSTRACT FROM AUTHOR]
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- 2019
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6. On the power of epigenome-wide association studies using a disease-discordant twin design.
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Li, Weilong, Christiansen, Lene, Hjelmborg, Jacob, Baumbach, Jan, and Tan, Qihua
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GENOMES , *DNA methylation , *HUMAN genetic variation , *METHYLATION , *HUMAN microbiota - Abstract
Motivation Many studies have investigated the association between DNA methylation alterations and disease occurrences using two design paradigms, traditional case-control and disease-discordant twins. In the disease-discordant twin design, the affected twin serves as the case and the unaffected twin serves as the control. Theoretically the twin design takes advantage of controlling for the shared genetic make-up, but it is still highly debatable if and how much researchers may benefit from such a design over the traditional case-control design. Results In this study, we investigate and compare the power of both designs with simulations. A liability threshold model was used assuming that identical twins share the same genetic contribution with respect to the liability of complex human diseases. Varying ranges of parameters have been used to ensure that the simulation is close to real-world scenarios. Our results reveal that the disease-discordant twin design implies greater statistical power over the traditional case-control design. For diseases with moderate and high heritability (>0.3), the disease-discordant twin design allows for large sample size reductions compared to the ordinary case-control design. Our simulation results indicate that the discordant twin design is indeed a powerful tool for epigenetic association studies. Availability and implementation Computer scripts are available at https://github.com/zickyls/EWAS-Twin-Simulation. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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7. Surfactant protein-D, a potential mediator of inflammation in axial spondyloarthritis.
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Munk, Heidi L, Fakih, Dalia, Christiansen, Lene, Tan, Qihua, Christensen, Anne F, Ejstrup, Leif, Loft, Anne G, Junker, Kirsten, Kyvik, Kirsten O, and Jounblat, Rania
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SPONDYLOARTHROPATHIES ,AGE distribution ,CHROMATOGRAPHIC analysis ,DNA ,ENZYME-linked immunosorbent assay ,GENETIC polymorphisms ,GLYCOPROTEINS ,SEX distribution ,SMOKING ,HLA-B27 antigen ,BODY mass index ,VISUAL analog scale ,DISEASE duration ,GENOTYPES ,DIAGNOSIS - Abstract
Objectives Surfactant protein-D (SP-D), an innate immune defence molecule of the collectin family, is expressed in lungs and additional extrapulmonary epithelia. SP-D has immune modulatory and anti-microbial effects depending on its oligomerization. The ratio of high molecular weight (HMW): low molecular weight (LMW) SP-D in serum is mainly determined by the Met11Thr polymorphism (SNP rs721917). We aimed to study the SP-D serum level and the molecular size distribution in patients with untreated axial spondyloarthritis (axSpA) as compared with control subjects. Methods Thirty-four patients with disease modifier untreated axSpA according to the ASAS criteria, age 19–63 years, disease duration 3.9 (2.2–5.6) years were included. Demographics, smoking habits, HLA-B27 status, ASDAS, BASDAI, BASFI, BASMI and visual analogue scale scores were recorded. SP-D in serum was measured by ELISA. DNA was isolated from whole blood and single nucleotide polymorphism rs721917 was genotyped. SP-D molecular size distribution was determined using gel filtration chromatography. Results SP-D in serum did not differ between patients with axSpA and healthy controls, 1177 (869, 1536) vs 910 (494, 1682) (P = 0.35) and SP-D did not correlate with disease activity. However, the HMW/LMW ratio of SP-D in serum was significantly lower in axSpA, 0.38 (0.18, 0.53) compared with controls 1.49 (0.37, 3.24) when adjusting for the Met11Thr polymorphism, gender, age, BMI and smoking (P = 0.0004). There was no correlation between HMW/LMW ratio and CRP or composite diseases outcome measures. Conclusion We suggest that predominance of LMW oligomeric variants of SP-D may enhance local or systemic inflammatory responses in axSpA. [ABSTRACT FROM AUTHOR]
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- 2018
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8. AFROPOLITANISM, CELEBRITY POLITICS, AND ICONIC IMAGINATIONS OF NORTH-SOUTH RELATIONS.
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RICHEY, LISA ANN and CHRISTIANSEN, LENE BULL
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HUMANITARIANISM ,AFRICAN diaspora ,COSMOPOLITANISM ,CELEBRITIES ,SOCIAL advocacy ,DEMOCRACY ,TRANSNATIONALISM - Abstract
'Afropolitanism' has become a disputed term referring to diverse engagements by Africans who are typically members of the cultural elite and participate in diaspora politics, online activism, fashion and literature debates. Simultaneously, in discussions of development aid, celebrity has become a way of mediating between proximity and distance in imagining relationships between South and North. Afropolitanism can be usefully considered as an Africa-specific, post-colonial form of cosmopolitanism that spans discourses of elite pan-African culture to theories of elite global aid culture. We argue that there are essential connections between the rise of Afropolitanism and the celebritization of North-South relations. In this realm, 'Afropolitanism' is an idea combining cosmopolitanism's notions of kindness to strangers in a world where the 'kindness' is aid and the 'strangers' are Africans. We analyse two archetypical Afropolitan performances by Danish aid celebrities to argue that their representations of Africa's external relations are theoretically more interesting, and politically more dangerous, than is currently understood. In doing so, we expand the debates around Afropolitanism and celebritization from the realm of cultural politics to one of International Relations. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Cohort Profile: The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies - secular trends in the health and functioning of the very old.
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Rasmussen, Signe Høi, Andersen-Ranberg, Karen, Thinggaard, Mikael, Jeune, Bernard, Skytthe, Axel, Christiansen, Lene, Vaupel, James W., McGue, Matt, and Christensen, Kaare
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BIRTH rate ,HEALTH of older people ,DEMOGRAPHIC change ,WORLD War II ,PUBLIC welfare - Published
- 2017
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10. Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density.
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Morris, John A, Tsai, Pei-Chien, Joehanes, Roby, Zheng, Jie, Trajanoska, Katerina, Soerensen, Mette, Forgetta, Vincenzo, Castillo-Fernandez, Juan Edgar, Frost, Morten, Spector, Tim D, Christensen, Kaare, Christiansen, Lene, Rivadeneira, Fernando, Tobias, Jonathan H, Evans, David M, Kiel, Douglas P, Hsu, Yi-Hsiang, Richards, J Brent, and Bell, Jordana T
- Abstract
ABSTRACT Genetic and environmental determinants of skeletal phenotypes such as bone mineral density (BMD) may converge through the epigenome, providing a tool to better understand osteoporosis pathophysiology. Because the epigenetics of BMD have been largely unexplored in humans, we performed an epigenome-wide association study (EWAS) of BMD. We undertook a large-scale BMD EWAS using the Infinium HumanMethylation450 array to measure site-specific DNA methylation in up to 5515 European-descent individuals ( N
Discovery = 4614, NValidation = 901). We associated methylation at multiple cytosine-phosphate-guanine (CpG) sites with dual-energy X-ray absorptiometry (DXA)-derived femoral neck and lumbar spine BMD. We performed sex-combined and stratified analyses, controlling for age, weight, smoking status, estimated white blood cell proportions, and random effects for relatedness and batch effects. A 5% false-discovery rate was used to identify CpGs associated with BMD. We identified one CpG site, cg23196985, significantly associated with femoral neck BMD in 3232 females ( p = 7.9 × 10−11 ) and 4614 females and males ( p = 3.0 × 10−8 ). cg23196985 was not associated with femoral neck BMD in an additional sample of 474 females ( p = 0.64) and 901 males and females ( p = 0.60). Lack of strong consistent association signal indicates that among the tested probes, no large-effect epigenetic changes in whole blood associated with BMD, suggesting future epigenomic studies of musculoskeletal traits measure DNA methylation in a different tissue with extended genome coverage. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]- Published
- 2017
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11. Genetic Influence on the Peripheral Blood CD4+ T-cell Differentiation Status in CMV Infection.
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Goldeck, David, Larsen, Lisbeth Aagaard, Christiansen, Lene, Christensen, Kaare, Hamprecht, Klaus, Pawelec, Graham, and Derhovanessian, Evelyna
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CYTOMEGALOVIRUS diseases ,HERPESVIRUS diseases ,CELL differentiation ,T cells ,HUMORAL immunity ,HERITABILITY ,AGING ,COMPARATIVE studies ,FLOW cytometry ,IMMUNOBLOTTING ,IMMUNOGLOBULINS ,LONGEVITY ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,PHENOTYPES ,EVALUATION research ,ANTIBODY formation - Abstract
A latent infection with cytomegalovirus (CMV), a ubiquitous beta herpesvirus, is associated with an accumulation of late-differentiated memory T-cells, often accompanied by a reciprocal reduced frequency of early-differentiated cells (commonly also referred to as "naïve"). However, this impact of CMV on T-cell phenotypes is variable between individuals. Our previous findings in a subgroup of participants in the Leiden familial Longevity Study indicated an important role of genetics. For further testing, we have analyzed middle-aged monozygotic (MZ, n = 42) and dizygotic (DZ, n = 39) twin pairs from the Danish Twin Registry for their T-cell differentiation status, assessed by surface expression of CD27, CD28, CD57, and KLRG-1. We observed a significant intraclass correlation between cotwins of MZ, but not DZ pairs for the differentiation status of CD4+ and CD8+ subsets. Classical heritability analysis confirmed a substantial contribution of genetics to the differentiation status of T-cells in CMV infection. The humoral (IgG) response to different CMV antigens also seems to be genetically influenced, suggesting that a similar degree of immune control of the virus in MZ twins might be responsible for their similar T-cell differentiation status. Thus, the way T-cells differentiate in the face of a latent CMV infection, and the parallel humoral responses, both controlling the virus, are genetically influenced. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group.
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Mengel-From, Jonas, Soerensen, Mette, Nygaard, Marianne, McGue, Matt, Christensen, Kaare, and Christiansen, Lene
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COGNITIVE ability ,CENTRAL nervous system ,GROWTH factors ,HAPLOTYPES ,HUMAN genetic variation ,COGNITION disorders diagnosis ,ACADEMIC medical centers ,GERIATRIC assessment ,AGING ,ALLELES ,COGNITION ,COGNITION disorders ,GENES ,GENETIC polymorphisms ,GLYCOSIDASES ,LONGITUDINAL method ,PSYCHOLOGICAL tests ,GENOTYPES - Abstract
Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes, for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously reported KL-VS had poorer cognitive function than noncarriers. Two other variants positioned in the 5' end of the gene, rs398655 and rs562020, were associated with better cognitive function independently of KL-VS, and the common haplotype AG was associated with poorer cognition, consistently across two cognitive measures in two cohort strata. The haplotype effect was stronger than that of KL-VS. Two variants, rs2283368 and rs9526984, were the only variants significantly associated with cognitive decline over 7 years. We discuss an age-dependent effect of KL and the possibility that multiple gene variants in KL are important for cognitive function among the oldest old participants. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort.
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Tan, Qihua, Heijmans, Bastiaan T, Hjelmborg, Jacob V B, Soerensen, Mette, Christensen, Kaare, and Christiansen, Lene
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AGING ,COMPARATIVE studies ,DNA ,GENES ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,REGRESSION analysis ,RESEARCH ,SURVIVAL analysis (Biometry) ,EVALUATION research ,CROSS-sectional method ,DNA methylation ,SEQUENCE analysis - Abstract
Background: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on the dynamic patterns in epigenetic changes during the aging process.Methods: We performed an epigenome-wide association study of intra-individual longitudinal changes in DNA methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake 73-82 years). Biological pathway analysis and survival analysis were also conducted on CpGs showing longitudinal change in their DNA-methylation levels. Classical twin models were fitted to each CpG site to estimate the genetic and environmental effects on DNA-methylation.Results: Our analysis identified 2284 CpG sites whose DNA-methylation levels changed longitudinally over the follow-up. Twin modelling revealed that the longitudinal change for 90% of these CpG sites was explained solely by individual unique environmental factors and only for 10% of these sites was it influenced by familial factors (genetic or shared environment). Over 60% of the identified CpG sites were replicated (same direction and replication P < 0.05) in an independent cross-sectional sample of 300 twins aged from 30 to 74 years. The replication rate went up to 91% for the top 53 CpGs with P < 1 × 10-07. Pathway analysis of genes linked to these CpGs identified biologically meaningful gene-sets involved in cellular-signalling events and in transmission across chemical synapses, which are important molecular underpinnings of aging-related degenerative disorders.Conclusion: Our epigenome-wide association studies on a cohort of old twins followed up for 10 years identified highly replicable epigenetic biomarkers predominantly implicated in signalling pathways of degenerative disorders and survival in the elderly. [ABSTRACT FROM AUTHOR]- Published
- 2016
14. Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort.
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Qihua Tan, Heijmans, Bastiaan T., Hjelmborg, Jacob v B., Soerensen, Mette, Christensen, Kaare, and Christiansen, Lene
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GENETICS of aging ,HUMAN genome ,DNA methylation ,BIOMARKERS ,PREDICTION models - Abstract
Background: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on the dynamic patterns in epigenetic changes during the aging process. Methods: We performed an epigenome-wide association study of intra-individual longitudinal changes in DNA methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake 73-82 years). Biological pathway analysis and survival analysis were also conducted on CpGs showing longitudinal change in their DNA-methylation levels. Classical twin models were fitted to each CpG site to estimate the genetic and environmental effects on DNA-methylation. Results: Our analysis identified 2284 CpG sites whose DNA-methylation levels changed longitudinally over the follow-up. Twin modelling revealed that the longitudinal change for 90% of these CpG sites was explained solely by individual unique environmental factors and only for 10% of these sites was it influenced by familial factors (genetic or shared environment). Over 60% of the identified CpG sites were replicated (same direction and replication P<0.05) in an independent cross-sectional sample of 300 twins aged from 30 to 74 years. The replication rate went up to 91% for the top 53 CpGs with P<1 10-07. Pathway analysis of genes linked to these CpGs identified biologically meaningful gene-sets involved in cellular-signalling events and in transmission across chemical synapses, which are important molecular underpinnings of aging-related degenerative disorders. Conclusion: Our epigenome-wide association studies on a cohort of old twins followed up for 10 years identified highly replicable epigenetic biomarkers predominantly implicated in signalling pathways of degenerative disorders and survival in the elderly. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Birth Weight and Adult Bone Metabolism Are Unrelated: Results From Birth Weight-Discordant Monozygotic Twins.
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Frost, Morten, Petersen, Inge, Andersen, Thomas L, Langdahl, Bente L, Buhl, Thora, Christiansen, Lene, Brixen, Kim, and Christensen, Kaare
- Abstract
ABSTRACT Low birth weight (BW) has been associated with poor bone health in adulthood. The aim of this study was to investigate the association between BW and bone mass and metabolism in adult BW-discordant monozygotic (MZ) twins. A total of 153 BW-extremely discordant MZ twin pairs were recruited from the Danish Twin Registry. Serum vitamin D (25-hydroxyvitamin D [25OHD]) and bone turnover markers (BTMs) amino-terminal propeptide of type I procollagen (P1NP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), and cross-linked C-telopeptide (CTX) were quantified. Femoral neck (FN), total hip (TH), lumbar spine (LS), and whole-body (WB) bone mineral density (BMD) (ie, FN-BMD, TH-BMD, LS-BMD, and WB-BMD, respectively) were measured using dual-energy X-ray absorptiometry (DXA). Twins were studied as single individuals using regression analyses with or without adjustment for height, weight, age, sex, and intrapair correlation. Within-pair differences were assessed using Student's t test and fixed-regression models. BW was not associated with BTMs, LS-BMD, TH-BMD, FN-BMD, or WB-BMD, but BW was associated with WB-BMC, and WB-Area after adjustments. Compared to the co-twin, twins with the highest BW were heavier and taller in adulthood (mean differences ± SD): 3.0 ± 10.5 kg; 1.6 ± 2.6 cm; both p < 0.001). Within-pair analyses showed that LS-BMD, TH-BMD, and FN-BMD tended to be higher in twins with highest BW (for all: mean difference 0.01 ± 0.1 g/cm
2 ; p = 0.08, 0.05, and 0.10, respectively). No difference was observed after adjustment for adult body size. Intrapair differences in BW were not associated with differences in any of the biochemical parameters or BMD. Small differences between twins in BMD were explained by dissimilarities in body size. These results suggest that BW and adult bone metabolism are unrelated. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]- Published
- 2013
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16. Personality Factors in the Long Life Family Study.
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Andersen, Stacy L., Sun, Jenny X., Sebastiani, Paola, Huntly, Jaimie, Gass, Jesse D., Feldman, Lori, Bae, Harold, Christiansen, Lene, and Perls, Thomas T.
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FAMILIES ,LONGEVITY ,PERSONALITY ,QUESTIONNAIRES ,RESEARCH funding ,STATISTICS ,DATA analysis ,REPEATED measures design ,CROSS-sectional method ,DESCRIPTIVE statistics - Published
- 2013
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17. Effects of the APOE {varepsilon}2 Allele on Mortality and Cognitive Function in the Oldest Old.
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Lindahl-Jacobsen, Rune, Tan, Qihua, Mengel-From, Jonas, Christensen, Kaare, Nebel, Almut, and Christiansen, Lene
- Abstract
Some studies indicate that the APOE 2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE 2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found no protective effect of the APOE 2 allele on mortality compared with the APOE 3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE 2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes. We did not find a protective effect of the APOE 2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE 4 carriers. The APOE 2 allele may be protective on cognitive decline among the oldest old. [ABSTRACT FROM AUTHOR]
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- 2013
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18. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old.
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Lindahl-Jacobsen, Rune, Tan, Qihua, Mengel-From, Jonas, Christensen, Kaare, Nebel, Almut, and Christiansen, Lene
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OLDER people ,GERIATRIC assessment ,COGNITIVE ability ,MORTALITY ,LONGEVITY - Abstract
Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes. We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old. [ABSTRACT FROM PUBLISHER]
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- 2013
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19. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.
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Mangino, Massimo, Hwang, Shih-Jen, Spector, Timothy D., Hunt, Steven C., Kimura, Masayuki, Fitzpatrick, Annette L., Christiansen, Lene, Petersen, Inge, Elbers, Clara C., Harris, Tamara, Chen, Wei, Srinivasan, Sathanur R., Kark, Jeremy D., Benetos, Athanase, El Shamieh, Said, Visvikis-Siest, Sophie, Christensen, Kaare, Berenson, Gerald S., Valdes, Ana M., and Viñuela, Ana
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- 2012
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20. A Meta-analysis of Four Genome-Wide Association Studies of Survival to Age 90 Years or Older: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
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Newman, Anne B., Walter, Stefan, Lunetta, Kathryn L., Garcia, Melissa E., Slagboom, P. Eline, Christensen, Kaare, Arnold, Alice M., Aspelund, Thor, Aulchenko, Yurii S., Benjamin, Emelia J., Christiansen, Lene, D'Agostino, Ralph B., Fitzpatrick, Annette L., Franceschini, Nora, Glazer, Nicole L., Gudnason, Vilmundur, Hofman, Albert, Kaplan, Robert, Karasik, David, and Kelly-Hayes, Margaret
- Subjects
AGING ,GENETICS of longevity ,GENETIC research ,LIFE spans - Abstract
Background.: Genome-wide association studies (GWAS) may yield insights into longevity. Methods. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/ Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n - 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n - 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. Results. There were 273 single-nucleotide polymorphism
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- 2010
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21. Commonly Studied Polymorphisms in Inflammatory Cytokine Genes Show Only Minor Effects on Mortality and Related Risk Factors in Nonagenarians.
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Dato, Serena, Krabbe, Karen S., Thinggaard, Mikael, Pedersen, Bente K., Christensen, Kaare, Bruunsgaard, Helle, and Christiansen, Lene
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GENETIC polymorphisms ,INFLAMMATORY mediators ,FUNCTIONAL loss in older people ,CYTOKINE genetics ,PHYSIOLOGY ,DISEASE risk factors - Abstract
Systemic low-grade inflammation is consistently associated with functional status, cognitive functioning, multimorbidity, and survival in oldest olds. If inflammation is either a cause or a consequence of age-related pathology, genetic determinants of late-life survival can reside in cytokine genes polymorphisms, regulating inflammatory responses. The aim of this study was to test associations between commonly studied polymorphisms in interleukin (IL)6, IL10, IL15, and IL18, and tumor necrosis factor-α genes and late-life survival in a longitudinal cohort of nonagenarians: the Danish 1905 cohort. Additionally, associations were investigated between inflammatory markers and major predictors of mortality as cognitive and functional status. Modest sex-specific associations were found with survival, cognitive functioning, and handgrip strength. Evaluation of combined genotypes indicated that, in nonagenarian men, the balance of pro- and anti-inflammatory activity at IL18 and IL10 loci is protective against cognitive decline. In conclusion, in this large study with virtually complete follow-up, commonly studied polymorphisms in cytokine genes do not have a major impact on late-life survival or associated risk phenotypes. [ABSTRACT FROM PUBLISHER]
- Published
- 2010
- Full Text
- View/download PDF
22. Methylenetetrahydrofolate Reductase 677C>T and Methionine Synthase 2756A>G Mutations: No Impact on Survival, Cognitive Functioning, or Cognitive Decline in Nonagenarians.
- Author
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Bathum, Lise, Von Bornemann Hjelmborg, Jacob, Christiansen, Lene, McGue, Matt, Jeune, Bernard, and Christensen, Kaare
- Subjects
HOMOCYSTEINE ,COGNITION in old age ,GENETIC polymorphisms ,METHYLENETETRAHYDROFOLATE reductase ,COGNITIVE ability - Abstract
Background. Several reports have shown an association between homocysteine, cognitive functioning, and survival among the oldest-old. Two common polymorphisms in the genes coding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and methionine synthase (MTR 2756A>G) have an impact on plasma homocysteine level. Methods. We examined the effect of the MTHFR 677C>T and MTR 2756A>G genotypes on baseline cognitive functioning, cognitive decline over 5 years measured in three assessments, and survival in a population-based cohort of 1581 nonagenarians. Cognitive functioning was assessed by using the Mini-Mental State Examination (MMSE) and five brief cognitive tests (cognitive composite). Results. There are no differences in MMSE score (p = .83) or in cognitive composite (p = .56) at intake as a function of genotype tested by analysis of variance, whereas sex and social group have a impact on MMSE (p < .03), and social group on the cognitive composite (p < .01). The mean MMSE was lower for women than for men. However, considering the group participating in all three assessments, there were no sex-related differences in MMSE (p = .34). The cognitive decline in the group participating in all three assessments was investigated using regression models for the relationship between cognitive performance and genotype, age, sex, and social group and revealed no significant difference. Furthermore, the MTHFR 677T and MTR 2756A heterozygous and homozygous genotype had no significant impact on survival, with hazard ratios of 1.05 (95% confidence interval [CI], 0.93-1.17), 0.93 (95% CI, 0.77-1.14), 1.05 (95% CI, 0.94-1.18), and 0.97 (95% CI, 0.74-1.28). Conclusions. MTHFR and MTR genotypes are not associated with cognitive functioning, cognitive decline, or survival among nonagenarians. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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23. Genetic Association Analysis of Human Longevity in Cohort Studies of Elderly Subjects: An Example of the PON1 Gene in the Danish 1905 Birth Cohort.
- Author
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Qihua Tan, Christiansen, Lene, Bathum, Lise, Shuxia Li, Kruse, Torben A., and Christensen, Xaare
- Subjects
- *
HUMAN genetic variation , *GENOTYPE-environment interaction , *LONGEVITY , *REGRESSION analysis , *DANES - Abstract
Although the case-control or the cross-sectional design has been popular in genetic association studies of human longevity, such a design is prone to false positive results due to sampling bias and a potential secular trend in gene-environment interactions. To avoid these problems, the cohort or follow-up study design has been recommended. With the observed individual survival information, the Cox regression model has been used for single-locus data analysis. In this article, we present a novel survival analysis model that combines population survival with individual genotype and phenotype information in assessing the genetic association with human longevity in cohort studies. By monitoring the changes in the observed genotype frequencies over the follow-up period in a birth cohort, we are able to assess the effects of the genotypes and/or haplotypes on individual survival. With the estimated parameters, genotype- and/or haplotype-specific survival and hazard functions can be calculated without any parametric assumption on the survival distribution. In addition, our model estimates haplotype frequencies in a birth cohort over the follow-up time, which is not observable in the multilocus genotype data. A computer simulation study was conducted to specifically assess the performance and power of our haplotype-based approach for given risk and frequency parameters under different sample sizes. Application of our method to paraoxonase genotype data detected a haplotype that significantly reduces carriers' hazard of death and thus reveals and stresses the important role of genetic variation in maintaining human survival at advanced ages. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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24. The catalase -262C/T promoter polymorphism and aging phenotypes.
- Author
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Christiansen, Lene, Petersen, Hans Christian, Bathum, Lise, Frederiksen, Henrik, McGue, Matt, and Christensen, Kaare
- Abstract
A low level of the central antioxidant enzyme catalase has been suggested to be a risk factor for diseases influenced by oxidative stress. In this study, we investigated the possible association of the catalase -262C/T polymorphism with survival, physical and cognitive functioning, and a number of oxidative stress-mediated disorders. The study population was 2223 Danish individuals, aged 45-93 years, drawn from three population-based surveys. The results suggest that the catalase -262C/T polymorphism is not associated with either survival, or the majority of the age-related phenotypes investigated. However, our data indicate a statistical significant association of TT homozygosity with improved physical functioning as well as a trend of the T allele conferring an improved general cognitive functioning, although these results did not remain significant after correcting for multiple testing. The results raise the hypothesis that the catalase -262T allele serves as protection against neurodegenerative and physical decline, although replication in other studies is warranted for confirmation of these findings. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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25. Data Resource Profile: The Copenhagen Hospital Biobank (CHB).
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Sørensen, Erik, Christiansen, Lene, Wilkowski, Bartlomiej, Larsen, Margit H, Burgdorf, Kristoffer S, Thørner, Lise W, Nissen, Janna, Pedersen, Ole B, Banasik, Karina, Brunak, Søren, Bundgaard, Henning, Stefánsson, Hreinn, Stefánsson, Kari, Melbye, Mads, and Ullum, Henrik
- Subjects
- *
POISONING , *MEDICAL registries , *MEDICAL research , *PROGNOSIS , *PERSONAL identification numbers , *MEDICAL record linkage , *BIOLOGICAL specimens , *HOSPITALS , *TISSUE banks - Published
- 2021
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26. Sultamicillin—a new antibiotic in the treatment of persistent lower respiratory tract infections caused by Haemophilus influenzae.
- Author
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Pressler, Tania, Pedersen, Svend Stenvang, Christiansen, Lene, Szaff, Marta, Koch, Christian, and Hoiby, Niels
- Abstract
is a frequent cause of recurrent or chronic lower respiratory tract infections in patients suffering from cystic fibrosis (CF) and other chronic obstructive pulmonary disease (COPD). Ampicillin and its derivatives are routinely used in treatment, but resistant strains producing β-lactamase frequently necessitate the use of other antibiotics. Sultamicillin is a compound agent for oral use in which ampicillin and the β-lactamase inhibitor sulbactam are linked as a double ester. This combination is active against many β-lactamase producing bacteria including ampicillin-resistant . Eight CF children and ten children with other COPD suffering from chronic or recurrent infection of the lower respiratory tract were treated with sultamicillin orally, 25 mg/kg, 12-hourly, for two weeks. Nine infections were caused by ampicillin-resistant strains. At the end of the treatment 65% of the patients were free of . The only adverse reaction was diarrhoea which occurred in 14 patients, and necessitated withdrawal of one patient from the study. [ABSTRACT FROM PUBLISHER]
- Published
- 1986
27. Handling blood cell composition in epigenetic studies on ageing.
- Author
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Qihua Tan, Heijmans, Bastiaan T., Hjelmborg, Jacob V. B., Soerensen, Mette, Christensen, Kaare, Christiansen, Lene, and Tan, Qihua
- Subjects
BLOOD cells ,DNA methylation ,BIOPSY ,AGING ,GENES ,EPIGENOMICS - Published
- 2017
- Full Text
- View/download PDF
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