Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

Skytthe, Axel; Valensin, Silvana; Jeune, Bernard; Cevenini, Elisa; Balard, Frédéric; Beekman, Marian; Bezrukov, Vladislav; Blanché, Hélène; Bolund, Lars; Broczek, Katarzyna; Carru, Ciriaco; Christensen, Kaare; Christiansen, Lene; Collerton, Joanna; Cotichini, Rodolfo; Craen, Anton J. M. de; Dato, Serena; Davies, Karen; Benedictis, G. De; Deiana, Luca; Flachsbart, Friederike; Gampe, Jutta; Gilbault, C.; Gonos, Efsthatios; Haimes, Erica; Hervonen, A.; Hurme, Mikko; Janiszewska, Dorota; Jylhä, Marja; Kirkwood, Tom; Kristensen, Peter; Laiho, Päivi; Leon, Alberta; Marchisio, A.; Masciulli, R.; Nebel, Almut; Passarino, Giuseppe; Pelicci, Gabrielle; Peltonen, Leena; Perola, Markus; Poulain, Michel; Rea, Irene Maeve; Remacle, José; Robine, Jean-Marie; Schreiber, Stefan; Scurti, Maria; Sevini, Federica; Sikora, Ewa; Skouteri, A.; Slagboom, P. Eline; Spazzafumo, Liana; Stazi, Maria Antonietta; Toccaceli, Virgilia; Toussaint, Olivier; Törnwall, Outi; Vaupel, James W.; Voutetakis, Konstantinos; Franceschi, Claudio

doi:10.1016/j.exger.2011.08.005

Cited by 53 publications

(34 citation statements)

References 15 publications

(14 reference statements)

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“…Here follows a brief outline of the inclusion procedure: The identification of offspring from long-lived families was undertaken in three nationwide, consecutive studies in Denmark, for which recruitment ran sequentially during the years 2004 to 2009: a pilot study: Danish Oldest Siblings (DOS) pilot study, the Genetics of Healthy Aging (GeHA) study [27], and the Long Life Family Study (LLFS) [28]. …”

Section: Methodsmentioning

confidence: 99%

Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Pedersen

Skytthe

Honig

et al. 2015

Annals of Epidemiology

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Purpose 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+. The offspring of the long-lived siblings were followed 1968–2009. Using high quality registry data, observed numbers of cancers were compared to 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 (SIRs) (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 to 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.

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Section: Methodsmentioning

confidence: 99%

Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Pedersen

Skytthe

Honig

et al. 2015

Annals of Epidemiology

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“…The oldest member of the sib-ship was defined as the "proband" ). The details of the design, recruitment and data management of the GEHA project were reported in a recent paper by Skytthe et al (Skytthe et al 2011). Briefly, the lists of sib pairs with individuals aged 90 years or more were provided by the local Population Register Offices, then families were contacted by mail and telephone to explain them the aim of the GEHA project and the procedure for participation.…”

Section: Study Populationmentioning

confidence: 99%

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing)

Cevenini¹,

Cotichini²,

Stazi³

et al. 2013

AGE

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In a scenario of increasing life expectancy worldwide, it is mandatory to identify the characteristics of a healthy aging phenotype, including survival predictors, and to disentangle those related to environment/ lifestyle versus those related to familiarity/genetics. To this aim we comprehensively characterised a cohort of 1,160 Italian subjects of 90 years and over (90+, mean age 93 years; age range 90-106 years) followed for 6 years survival, belonging to 552 sib-ships (familiar longevity) recruited (2005)(2006)(2007)(2008) within the EU-funded GEHA project in three Italian geographic areas (Northern, Central and Southern Italy) different for urban/rural and socio-economical characteristics. On the whole, the following factors emerged as significant predictors of survival after 90 years of age: absence of cognitive impairment and physical disability, high hand grip strength scores and body mass index (BMI) values, "excellent/good" self-reported health, high haemoglobin and total cholesterol levels and low creatinine levels. These parameters, excluding BMI values, were also significantly associated within sib-ships, suggesting a strong familial/genetic component. Geographical micro-heterogeneity of survival predictors emerged, such as functional and physical status being more important in Southern than in Central and Northern Italy. In conclusion, we identified modifiable survival predictors related to specific domains, whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the GEHA project, whose major aim is the comprehensive evaluation of phenotypic and genetic data.

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“…In this paper, we performed genome-wide linkage analysis among 2118 European nonagenarian sibships of the Genetics of Healthy Ageing (GEHA) Study (Franceschi et al , 2007; Skytthe et al , 2011). This integrated European project was initiated in 2004 with the aim of identifying genes involved in healthy ageing and longevity.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide linkage analysis for human longevity: Genetics of Healthy Aging Study

et al. 2013

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Summary Clear evidence exists for heritability of human longevity, 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 2118 nonagenarian Caucasian sibling pairs that have been enrolled in fifteen study centers of eleven European countries as part of the Genetics of Healthy Ageing (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 1,228 unrelated nonagenarian and 1,907 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 APOEε4 and APOEε2 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. Since the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.

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Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

Cited by 53 publications

References 15 publications

Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing)

Genome‐wide linkage analysis for human longevity: Genetics of Healthy Aging Study

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