Browsing by Author "McGue, Matt"
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Item Open Access Cohort Profile: The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies - secular trends in the health and functioning of the very old.(Int J Epidemiol, 2017-04-22) Rasmussen, Signe Høi; Andersen-Ranberg, Karen; Thinggaard, Mikael; Jeune, Bernard; Skytthe, Axel; Christiansen, Lene; Vaupel, James W; McGue, Matt; Christensen, KaareItem Open Access DNA methylation age is associated with mortality in a longitudinal Danish twin study.(Aging Cell, 2016-02) Christiansen, Lene; Lenart, Adam; Tan, Qihua; Vaupel, James W; Aviv, Abraham; McGue, Matt; Christensen, KaareAn epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1) times per 5-year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging.Item Open Access Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.(Age (Dordr), 2013-04) Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea; Beekman, Marian; Suchiman, H Eka D; Jacobsen, Rune; McGue, Matt; Stevnsner, Tinna; Bohr, Vilhelm A; de Craen, Anton JM; Westendorp, Rudi GJ; Schreiber, Stefan; Slagboom, P Eline; Nebel, Almut; Vaupel, James W; Christensen, Kaare; Christiansen, LeneIn this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.Item Open Access Genetic diversity fuels gene discovery for tobacco and alcohol use.(Nature, 2022-12) Saunders, Gretchen RB; Wang, Xingyan; Chen, Fang; Jang, Seon-Kyeong; Liu, Mengzhen; Wang, Chen; Gao, Shuang; Jiang, Yu; Khunsriraksakul, Chachrit; Otto, Jacqueline M; Addison, Clifton; Akiyama, Masato; Albert, Christine M; Aliev, Fazil; Alonso, Alvaro; Arnett, Donna K; Ashley-Koch, Allison E; Ashrani, Aneel A; Barnes, Kathleen C; Barr, R Graham; Bartz, Traci M; Becker, Diane M; Bielak, Lawrence F; Benjamin, Emelia J; Bis, Joshua C; Bjornsdottir, Gyda; Blangero, John; Bleecker, Eugene R; Boardman, Jason D; Boerwinkle, Eric; Boomsma, Dorret I; Boorgula, Meher Preethi; Bowden, Donald W; Brody, Jennifer A; Cade, Brian E; Chasman, Daniel I; Chavan, Sameer; Chen, Yii-Der Ida; Chen, Zhengming; Cheng, Iona; Cho, Michael H; Choquet, Hélène; Cole, John W; Cornelis, Marilyn C; Cucca, Francesco; Curran, Joanne E; de Andrade, Mariza; Dick, Danielle M; Docherty, Anna R; Duggirala, Ravindranath; Eaton, Charles B; Ehringer, Marissa A; Esko, Tõnu; Faul, Jessica D; Fernandes Silva, Lilian; Fiorillo, Edoardo; Fornage, Myriam; Freedman, Barry I; Gabrielsen, Maiken E; Garrett, Melanie E; Gharib, Sina A; Gieger, Christian; Gillespie, Nathan; Glahn, David C; Gordon, Scott D; Gu, Charles C; Gu, Dongfeng; Gudbjartsson, Daniel F; Guo, Xiuqing; Haessler, Jeffrey; Hall, Michael E; Haller, Toomas; Harris, Kathleen Mullan; He, Jiang; Herd, Pamela; Hewitt, John K; Hickie, Ian; Hidalgo, Bertha; Hokanson, John E; Hopfer, Christian; Hottenga, JoukeJan; Hou, Lifang; Huang, Hongyan; Hung, Yi-Jen; Hunter, David J; Hveem, Kristian; Hwang, Shih-Jen; Hwu, Chii-Min; Iacono, William; Irvin, Marguerite R; Jee, Yon Ho; Johnson, Eric O; Joo, Yoonjung Y; Jorgenson, Eric; Justice, Anne E; Kamatani, Yoichiro; Kaplan, Robert C; Kaprio, Jaakko; Kardia, Sharon LR; Keller, Matthew C; Kelly, Tanika N; Kooperberg, Charles; Korhonen, Tellervo; Kraft, Peter; Krauter, Kenneth; Kuusisto, Johanna; Laakso, Markku; Lasky-Su, Jessica; Lee, Wen-Jane; Lee, James J; Levy, Daniel; Li, Liming; Li, Kevin; Li, Yuqing; Lin, Kuang; Lind, Penelope A; Liu, Chunyu; Lloyd-Jones, Donald M; Lutz, Sharon M; Ma, Jiantao; Mägi, Reedik; Manichaikul, Ani; Martin, Nicholas G; Mathur, Ravi; Matoba, Nana; McArdle, Patrick F; McGue, Matt; McQueen, Matthew B; Medland, Sarah E; Metspalu, Andres; Meyers, Deborah A; Millwood, Iona Y; Mitchell, Braxton D; Mohlke, Karen L; Moll, Matthew; Montasser, May E; Morrison, Alanna C; Mulas, Antonella; Nielsen, Jonas B; North, Kari E; Oelsner, Elizabeth C; Okada, Yukinori; Orrù, Valeria; Palmer, Nicholette D; Palviainen, Teemu; Pandit, Anita; Park, S Lani; Peters, Ulrike; Peters, Annette; Peyser, Patricia A; Polderman, Tinca JC; Rafaels, Nicholas; Redline, Susan; Reed, Robert M; Reiner, Alex P; Rice, John P; Rich, Stephen S; Richmond, Nicole E; Roan, Carol; Rotter, Jerome I; Rueschman, Michael N; Runarsdottir, Valgerdur; Saccone, Nancy L; Schwartz, David A; Shadyab, Aladdin H; Shi, Jingchunzi; Shringarpure, Suyash S; Sicinski, Kamil; Skogholt, Anne Heidi; Smith, Jennifer A; Smith, Nicholas L; Sotoodehnia, Nona; Stallings, Michael C; Stefansson, Hreinn; Stefansson, Kari; Stitzel, Jerry A; Sun, Xiao; Syed, Moin; Tal-Singer, Ruth; Taylor, Amy E; Taylor, Kent D; Telen, Marilyn J; Thai, Khanh K; Tiwari, Hemant; Turman, Constance; Tyrfingsson, Thorarinn; Wall, Tamara L; Walters, Robin G; Weir, David R; Weiss, Scott T; White, Wendy B; Whitfield, John B; Wiggins, Kerri L; Willemsen, Gonneke; Willer, Cristen J; Winsvold, Bendik S; Xu, Huichun; Yanek, Lisa R; Yin, Jie; Young, Kristin L; Young, Kendra A; Yu, Bing; Zhao, Wei; Zhou, Wei; Zöllner, Sebastian; Zuccolo, Luisa; 23andMe Research Team; Biobank Japan Project; Batini, Chiara; Bergen, Andrew W; Bierut, Laura J; David, Sean P; Gagliano Taliun, Sarah A; Hancock, Dana B; Jiang, Bibo; Munafò, Marcus R; Thorgeirsson, Thorgeir E; Liu, Dajiang J; Vrieze, ScottTobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Item Open Access Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory.(Behavior genetics, 2014-07) van den Berg, Stéphanie M; de Moor, Marleen HM; McGue, Matt; Pettersson, Erik; Terracciano, Antonio; Verweij, Karin JH; Amin, Najaf; Derringer, Jaime; Esko, Tõnu; van Grootheest, Gerard; Hansell, Narelle K; Huffman, Jennifer; Konte, Bettina; Lahti, Jari; Luciano, Michelle; Matteson, Lindsay K; Viktorin, Alexander; Wouda, Jasper; Agrawal, Arpana; Allik, Jüri; Bierut, Laura; Broms, Ulla; Campbell, Harry; Smith, George Davey; Eriksson, Johan G; Ferrucci, Luigi; Franke, Barbera; Fox, Jean-Paul; de Geus, Eco JC; Giegling, Ina; Gow, Alan J; Grucza, Richard; Hartmann, Annette M; Heath, Andrew C; Heikkilä, Kauko; Iacono, William G; Janzing, Joost; Jokela, Markus; Kiemeney, Lambertus; Lehtimäki, Terho; Madden, Pamela AF; Magnusson, Patrik KE; Northstone, Kate; Nutile, Teresa; Ouwens, Klaasjan G; Palotie, Aarno; Pattie, Alison; Pesonen, Anu-Katriina; Polasek, Ozren; Pulkkinen, Lea; Pulkki-Råback, Laura; Raitakari, Olli T; Realo, Anu; Rose, Richard J; Ruggiero, Daniela; Seppälä, Ilkka; Slutske, Wendy S; Smyth, David C; Sorice, Rossella; Starr, John M; Sutin, Angelina R; Tanaka, Toshiko; Verhagen, Josine; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Willemsen, Gonneke; Wright, Margaret J; Zgaga, Lina; Rujescu, Dan; Metspalu, Andres; Wilson, James F; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Deary, Ian J; Räikkönen, Katri; Arias Vasquez, Alejandro; Costa, Paul T; Keltikangas-Järvinen, Liisa; van Duijn, Cornelia M; Penninx, Brenda WJH; Krueger, Robert F; Evans, David M; Kaprio, Jaakko; Pedersen, Nancy L; Martin, Nicholas G; Boomsma, Dorret IMega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.Item Open Access Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies.(Exp Gerontol, 2012-05) Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea; Beekman, Marian; Jacobsen, Rune; Suchiman, H Eka D; de Craen, Anton JM; Westendorp, Rudi GJ; Schreiber, Stefan; Stevnsner, Tinna; Bohr, Vilhelm A; Slagboom, P Eline; Nebel, Almut; Vaupel, James W; Christensen, Kaare; McGue, Matt; Christiansen, LeneHere we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways. In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing. When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p<0.05), while rs9456497 (IGF2R) and rs1157146 (RAD52) showed non-significant tendencies, indicative of effects also in late life survival. In addition, rs207444 (XDH) presented the same direction of effect when inspecting the 6 SNPs from the longitudinal study in the case-control data, hence, suggesting an effect also in survival from middle age to old age. No formal replications were observed when investigating the 11 SNPs from the case-control study in 1613 oldest-old (age 95-110) and 1104 middle-aged Germans, although rs11571461 (RAD52) did show a supportive non-significant tendency (OR=1.162, 95% CI=0.927-1.457). The same was true for rs10047589 (TNXRD1) (HR=0.758, 95%CI=0.543-1.058) when examining the 6 SNPs from the longitudinal study in a Dutch longitudinal cohort of oldest-old (age 85+, N=563). In conclusion, the present candidate gene based association study, the largest to date applying a pathway approach, not only points to potential new longevity loci, but also underlines the difficulties of replicating association findings in independent study populations and thus the difficulties in identifying universal longevity polymorphisms.Item Open Access Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data.(Ann Epidemiol, 2015-08) Pedersen, Jacob K; Skytthe, Axel; McGue, Matt; Honig, Lawrence S; Franceschi, Claudio; Kirkwood, Thomas BL; Passarino, Giuseppe; Slagboom, P Eline; Vaupel, James W; Christensen, KaarePURPOSE: Familial clustering of longevity is well documented and includes both genetic and other familial factors, but the specific underlying mechanisms are largely unknown. We examined whether low incidence of specific cancers is a mechanism for familial clustering of longevity. METHODS: The study population of individuals from longevity-enriched families consisted of 3267 offspring from 610 Danish long-lived families defined by two siblings attaining an age of 90 years or more. The offspring of the long-lived siblings were followed from 1968 to 2009. Using high-quality registry data, observed numbers of cancers were compared with expected numbers based on gender-, calendar period-, and age-specific incidence rates in the general population. RESULTS: During the 41-year-follow-up period, a total of 423 cancers occurred in 397 individuals. The standardized incidence ratios (95% confidence interval) for offspring of long-lived individuals were 0.78 (0.70-0.86) for overall cancer; 0.66 (0.56-0.77) for tobacco-related cancer; 0.34 (0.22-0.51) for lung cancer; 0.88 (0.71-1.10) for breast cancer; 0.91 (0.62-1.34) for colon cancer. CONCLUSIONS: The low incidence of tobacco-related cancers in long-lived families compared with non-tobacco-related cancers suggests that health behavior plays a central role in lower early cancer incidence in offspring of long-lived siblings in Denmark.Item Open Access Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart.(Lancet, 2013-11-02) Christensen, Kaare; Thinggaard, Mikael; Oksuzyan, Anna; Steenstrup, Troels; Andersen-Ranberg, Karen; Jeune, Bernard; McGue, Matt; Vaupel, James WBACKGROUND: A rapidly increasing proportion of people in high-income countries are surviving into their tenth decade. Concern is widespread that the basis for this development is the survival of frail and disabled elderly people into very old age. To investigate this issue, we compared the cognitive and physical functioning of two cohorts of Danish nonagenarians, born 10 years apart. METHODS: People in the first cohort were born in 1905 and assessed at age 93 years (n=2262); those in the second cohort were born in 1915 and assessed at age 95 years (n=1584). All cohort members were eligible irrespective of type of residence. Both cohorts were assessed by surveys that used the same design and assessment instrument, and had almost identical response rates (63%). Cognitive functioning was assessed by mini-mental state examination and a composite of five cognitive tests that are sensitive to age-related changes. Physical functioning was assessed by an activities of daily living score and by physical performance tests (grip strength, chair stand, and gait speed). FINDINGS: The chance of surviving from birth to age 93 years was 28% higher in the 1915 cohort than in the 1905 cohort (6·50% vs 5·06%), and the chance of reaching 95 years was 32% higher in 1915 cohort (3·93% vs 2·98%). The 1915 cohort scored significantly better on the mini-mental state examination than did the 1905 cohort (22·8 [SD 5·6] vs 21·4 [6·0]; p<0·0001), with a substantially higher proportion of participants obtaining maximum scores (28-30 points; 277 [23%] vs 235 [13%]; p<0·0001). Similarly, the cognitive composite score was significantly better in the 1915 than in the 1905 cohort (0·49 [SD 3·6] vs 0·01 [SD 3·6]; p=0·0003). The cohorts did not differ consistently in the physical performance tests, but the 1915 cohort had significantly better activities of daily living scores than did the 1905 cohort (2·0 [SD 0·8] vs 1·8 [0·7]; p<0·0001). INTERPRETATION: Despite being 2 years older at assessment, the 1915 cohort scored significantly better than the 1905 cohort on both the cognitive tests and the activities of daily living score, which suggests that more people are living to older ages with better overall functioning. FUNDING: Danish National Research Foundation; US National Institutes of Health-National Institute on Aging; Danish Agency for Science, Technology and Innovation; VELUX Foundation.Item Open Access Physical and mental decline and yet rather happy? A study of Danes aged 45 and older.(Aging Ment Health, 2015) Vestergaard, Sonja; Thinggaard, Mikael; Jeune, Bernard; Vaupel, James W; McGue, Matt; Christensen, KaareOBJECTIVES: Little is known about whether the feeling of happiness follows the age-related decline in physical and mental functioning. The objective of this study was to analyze differences with age in physical and mental functions and in the feeling of happiness among Danes aged 45 years and older. METHOD: Three Danish population-based surveys including 11,307 participants aged 45+ years, of whom 2411 were in the age group of 90+, were conducted in the period 1995-2001. The participation rate in the three surveys was between 63% and 82% and the same design and the same instrument were used. Self-reported mobility, a cognitive composite score, and a depression symptomatology score including a question about happiness were assessed. T-score metric was used to compare across domains and age groups. RESULTS: Overall, successively older age groups performed worse than the youngest age group (45-49 years), and the estimated linear decline was greater after age 70 than before age 70. For example, when comparing the oldest age group (90+ years) with the youngest, the T-score differences were found to be the largest for the mobility score (men: 40.2, women: 41.4), followed by the cognitive function (men: 22.0, women: 24.9), and the total depression symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference in happiness was small (men: 5.6, women: 6.0). CONCLUSION: Despite markedly poorer physical and mental functions with increasing age, in this Danish sample age did not seem to affect happiness to a similarly notable extent, although, in this study, cohort and age effects cannot be disentangled.Item Open Access Sex differences in the level and rate of change of physical function and grip strength in the Danish 1905-cohort study.(J Aging Health, 2010-08) Oksuzyan, Anna; Maier, Heiner; McGue, Matt; Vaupel, James W; Christensen, KaareOBJECTIVE: The study was conducted to examine sex differences in the initial level and rate of change in physical function and grip strength. METHOD: The baseline survey included 2,262 Danes born in 1905 and alive in 1998 and followed-up in 2000, 2003, and 2005. Hence, the authors fully used the power of having a cohort with multiple assessments in late life and virtually complete follow-up of lifespan (through December 2008). Latent growth curve modeling was used. RESULTS: Men had higher initial levels and rates of decline in strength score and grip strength. Lifespan was positively correlated with intercepts and slopes. DISCUSSION: The Danish data suggested that the longest-living individuals have higher initial levels of strength score and grip strength and smaller rate of change. The data further suggested that the initial level of strength score and grip strength was more predictive of mortality than the rate of change was, and the predictive effects were similar in men and women.Item Open Access Survival Prognosis in Very Old Adults.(J Am Geriatr Soc, 2016-01) Thinggaard, Mikael; McGue, Matt; Jeune, Bernard; Osler, Merete; Vaupel, James W; Christensen, KaareOBJECTIVES: To determine whether simple functional indicators are predictors of survival prognosis in very old adults. DESIGN: In-person survey conducted over a 3-month period in 1998; assessment of survival over a 15-year follow-up period. SETTING: Denmark. PARTICIPANTS: All 3,600 Danes born in 1905 and living in Denmark in 1998, were invited to participate regardless of residence and health; 2,262 (63%) participated in the survey: 1,814 (80.2%) in person and 448 (19.8%) through a proxy. MEASUREMENTS: Socioeconomic factors, medications and diseases, activities of daily living, physical performance, cognition, depression symptomatology, self-rated health, and all-cause mortality, evaluated as average remaining lifespan and chance of surviving to 100 years. RESULTS: Men aged 92 to 93 had an overall 6.0% chance of surviving to 100 years, whereas the chance for women was 11.4%. Being able to rise without use of hands increased the chance for men to 11.2% (95% confidence interval (CI)=7.7-14.7) and for women to 22.0% (95% CI=18.9-25.1). When combining this with a Mini-Mental State Examination (MMSE) scores from 28 to 30, the chances were 21.7% (95% CI=11.5-31.9) for men and 34.2% (95% CI=24.8-43.5) for women. CONCLUSION: Chair stand score combined with MMSE score is a quick and easy way to estimate overall chance of survival in very old adults, which is particularly relevant when treatment with potential side effects for nonacute diseases is considered.Item Open Access The Danish Twin Registry: linking surveys, national registers, and biological information.(Twin Res Hum Genet, 2013-02) Skytthe, Axel; Christiansen, Lene; Kyvik, Kirsten Ohm; Bødker, Frans L; Hvidberg, Lars; Petersen, Inge; Nielsen, Morten MF; Bingley, Paul; Hjelmborg, Jacob; Tan, Qihua; Holm, Niels V; Vaupel, James W; McGue, Matt; Christensen, KaareOver the last 60 years, the resources and the research in the Danish Twin Registry (DTR) have periodically been summarized. Here, we give a short overview of the DTR and a more comprehensive description of new developments in the twenty-first century. First, we outline our experience over the last decade of combining questionnaire and survey data with national demographic, social, and health registers in Statistics Denmark. Second, we describe our most recent data collection effort, which was conducted during the period 2008-2011 and included both in-person assessments of 14,000+ twins born 1931-1969 and sampling of biological material, hereby expanding and consolidating the DTR biobank. Third, two examples of intensively studied twin cohorts are given. The new developments in the DTR in the last decade have facilitated the ongoing research and laid the groundwork for new research directions.