The Danish Twin Registry: Linking Surveys, National Registers, and Biological Information

Skytthe, Axel; Christiansen, Lene; Kyvik, Kirsten Ohm; Bødker, Frans L; Hvidberg, Lars; Petersen, Inge; Nielsen, Morten Meyerhoff; Bingley, Paul; Hjelmborg, Jacob; Tan, Qihua; Holm, Niels V.; Vaupel, James W.; Christensen, Kaare

doi:10.1017/thg.2012.77

Cited by 80 publications

(83 citation statements)

References 26 publications

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“…Briefly, the sample studied here included 1,089 cases (mean age: 93.1 years, age range 92.2–93.8 years, 29% males and 71% females) drawn from eligible members of the Danish 1905 Birth Cohort Study (Nybo et al., 2001) and 736 controls (mean age 50.6, age range 46.0–55.0, gender distribution 50% males and 50% females) from the Study of Middle Aged Danish Twins (MADT) (Skytthe et al., 2013). Information on survival status per 1st of January 2015 for the oldest‐old was retrieved from the Danish Central Population Register (Pedersen, Gotzsche, Moller & Mortensen, 2006).…”

Section: Methodsmentioning

confidence: 99%

The genetic component of human longevity: New insights from the analysis of pathway‐based SNP‐SNP interactions

et al. 2018

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SummaryIn human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin‐like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1,089 unrelated nonagenarians from the Danish 1905 Birth Cohort Study and 736 Danish controls aged 46–55 years) for evaluating synergic interactions by SNPsyn. Synergies were further tested by the multidimensional reduction (MDR) approach, both intra‐ and interpathways. The best combinations (FDR<0.0001) resulted those encompassing IGF1R‐rs12437963 and PTPN1‐rs6067484, TP53‐rs2078486 and ERCC2‐rs50871, TXNRD1‐rs17202060 and TP53‐rs2078486, the latter two supporting a central role of TP53 in mediating the concerted activation of the DNA repair and pro‐antioxidant pathways in human longevity. Results were consistently replicated with both approaches, as well as a significant effect on longevity was found for the GHSR gene, which also interacts with partners belonging to both IIS and DNA repair pathways (PAPPA,PTPN1,PARK7, MRE11A). The combination GHSR‐MREA11, positively associated with longevity by MDR, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP‐SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes of additional networks involved in human longevity.

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Section: Methodsmentioning

confidence: 99%

The genetic component of human longevity: New insights from the analysis of pathway‐based SNP‐SNP interactions

et al. 2018

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“…A total of 4,731 twins have completed an intake LSADT assessment comprising 1,152 pairs. Approximately 80% of the participants have provided blood spots and 689 twins, comprising 290 same-sexed pairs, provided full blood samples in 1997 (Skytthe et al, 2013). The data in the present study were based on intact pairs who participated in survey 2005.…”

Section: The Longitudinal Study Of Aging Danish Twins (Lsadt)mentioning

confidence: 99%

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

et al. 2015

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Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

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“…The registry contains information about twins born between 1870 and 2004, and it currently holds data on more than 86,000 Danish twin pairs [11]. Zygosity is self-reported and established through a questionnaire on the degree of similarity between twins in a pair.…”

Section: Methodsmentioning

confidence: 99%

“…Zygosity is self-reported and established through a questionnaire on the degree of similarity between twins in a pair. The validity of this classification has been evaluated through blood samples and the misclassification rate was found to be less than 5% [11]. …”

Section: Methodsmentioning

confidence: 99%

Myeloproliferative Neoplasms in Danish Twins

Andersen¹,

Bjerrum²,

Ranjan³

et al. 2018

Acta Haematol

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Objective: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases characterized by clonal hyperproliferation of immature and mature cells of the myeloid lineage. Genetic differences have been proposed to play a role in the development of MPNs. Monozygotic twin pairs with MPNs have been reported in a few case reports, but the MPN concordance pattern in twins remains unknown. Method: All twin pairs born in the period 1900–2010 were identified in the nationwide Danish Twin Registry. Only pairs with both twins alive on January 1, 1977, and those born thereafter were included to allow identification in the Danish National Patient Registry. Results: A total of 158 twin pairs were registered with an MPN diagnosis: 36 monozygotic, 104 dizygotic, and 18 pairs with unknown zygosity. MPNs were diagnosed in both twins in 4 pairs. The probandwise concordance rates for monozygotic twin pairs were higher than for dizygotic twin pairs (15 vs. 0%; p = 0.016). Conclusion: An estimated concordance rate of 15% (95% CI 0.059–0.31) is modest, but given the rarity of MPNs this finding is clinically relevant and provides further support for the role of genetic predisposition in the development of MPNs.

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The Danish Twin Registry: Linking Surveys, National Registers, and Biological Information

Cited by 80 publications

References 26 publications

The genetic component of human longevity: New insights from the analysis of pathway‐based SNP‐SNP interactions

The genetic component of human longevity: New insights from the analysis of pathway‐based SNP‐SNP interactions

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

Myeloproliferative Neoplasms in Danish Twins

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