Willemsen G.,VU University Amsterdam |
Ward K.J.,King's College London |
Bell C.G.,King's College London |
Christensen K.,University of Southern Denmark |
And 16 more authors.
Twin Research and Human Genetics | Year: 2015
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. Copyright © The Author(s) 2015.
PubMed | University of Sydney, Murcia Institute for Biomedical Research IMIB Arrixaca and University of Murcia
Type: | Journal: The spine journal : official journal of the North American Spine Society | Year: 2016
There is limited research investigating educational attainment as a risk factor for low back pain (LBP), with the influence of gender commonly being neglected. Furthermore, genetics and early shared environment explain a substantial proportion of LBP cases and need to be controlled for when investigating risk factors for LBP.To investigate whether educational attainment affects the prevalence and risk of LBP differently in males and females, while controlling for the influence of genetics and early shared environment.Cross-sectional and prospective twin case-control study.Adult monozygotic (MZ) and dizygotic (DZ) twins from the Murcia Twin Registry, with available data on educational attainment, formed the base sample for this study. The prevalence analysis considered twins with available data on LBP in 2013 (n=1,580). The longitudinal analysis considered twins free of LBP at baseline (2009/11), with available data on LBP at follow up (2013) (n=1,077).Data on the lifetime prevalence of activity limiting LBP (outcome) and educational attainment (risk factor) were self-reported.The prevalence analysis investigated the cross-sectional association between educational attainment and LBP, while the longitudinal analysis investigated whether educational attainment increased the risk of developing LBP. Both analyses were performed in the following sequence. First, a total sample analysis was performed on all twins (considering them as individuals), adjusting for confounding variables selected by the data. Second, to control for the influence of genetics and early shared environment a within-pair case-control analysis (stratified by zygosity) was performed on complete twin pairs discordant for LBP (i.e. one twin had LBP while the co-twin did not). All analyses were stratified for gender where possible, with an interaction term determining whether gender was a significant moderator of the association between educational attainment and LBP. The Murcia Twin Registry is supported by Fundacin Sneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08 & 15302/PHCS/10) and the Ministry of Science and Innovation, Spain (PSI11560-2009). Funding for this project has also been received from Fundacin MAPFRE (2012). The authors declare that there are no conflicts of interest.Females with either general secondary or university education were less likely to experience (prevalence analysis), or develop LBP (longitudinal analysis). Educational attainment did not affect the risk of LBP in males. When controlling for the effects of genetics and early shared environment the relationship between educational status and LBP in females was no longer statistically significant.Educational attainment affects LBP differently in males and females, with higher levels of education only decreasing the risk of developing LBP in females. After adjusting for genetics and early shared environment, the relationship between educational attainment and LBP in females disappears. This suggests genetics and early shared environment are confounding the relationship between educational attainment and LBP in females.