56 research outputs found
Twin studies of cardiorespiratory disease, daily cardiovascular activity and imaging
Twin studies have helped gain insight into the role of heritability in disease and disease processes. Given the large burden cardiorespiratory diseases place on society, these diseases have featured largely in twin studies. In part A of this chapter, a brief overview of the outcomes of such studies is provided for a wide variety of cardiovascular and respiratory diseases. A moderate to high influence of genes is seen for the vast majority of these diseases. This highlights the importance of screening high-risk individuals, as well as studying gene-by-environment interactions. While studying the disease itself is important, insight into the processes leading up to the disease may increase our understanding of disease development. By studying cardiovascular function for prolonged periods of time in nonpatient populations, valuable insights can be obtained in normal day cardiovascular functioning. In part B of this chapter, we review twin studies in which indices of cardiovascular function were recorded throughout the day and night using ambulatory monitoring. Here too, it is evident that heritability influences the variation of everyday blood pressure and heart action. Another way of gaining insight into the physiological processes underlying disease development is through imaging studies. In part C of this chapter, we discuss the inclusion of twins in imaging studies. Twin studies of imaging data are still sparse and cover a wide variety of traits. Studies including both monozygotic and dizygotic twins generally point to a role for genetic factors, though the degree differs across the traits. Within imaging studies, the twin discordant design is also often applied, demonstrating the occurrence of gene-by-environment interaction. Overall, twin studies have shown that genetic factors play an important role in individual variation in many physiological diseases and disease processes. Future studies are expected to provide more insight into the interplay of genetic and environmental factors with respect to physiological function and risk. Of particular interest are studies looking into epigenetic mechanisms, which are gradually emerging and may further help the development of more personalized medicine, based on genetic vulnerability as well as lifestyle and environment.</p
Association between personality profile and subclinical atherosclerosis: the role of genes and environment
Background. The mechanism underlying the association between personality profile and
subclinical atherosclerosis is poorly understood. This study explores the association between
personality, carotid atherosclerosis and arterial stiffness, and the contribution of genes and
environment to this association.
Methods. Early atherosclerotic traits, including carotid intima-media thickness (CCA-IMT),
aortic pulse wave velocity (PWVao) and heart rate, were assessed in 318 adult twins, who
also completed a Big Five personality questionnaire. Using the co-twin control approach, the
association between intra-pair differences in clinical and personality scores was assessed in
dizygotic (DZ) and monozygotic (MZ) twins separately.
Results. An association between CCA-IMT and extroverted personality, as well as between
PWVao and openness to experience was detected. The inverse association between CCAIMT
and extraversion was persistent in DZ and disappeared in MZ twins, suggesting genetic
confounding. In contrast, the association between PWVao and openness to experience was of
the same magnitude in DZ and MZ twins, thus surviving the adjustment for genetic and
shared environmental factors.
Conclusions. This study highlights that the association between some psychological factors
and cardiovascular traits may be partly explained by genetic factors. This result may provide
support for the feasibility of prevention programs based on assessing familiarity for
personality disorders to detect genetic risk for subclinical cardiovascular disease
Twin studies of cardiorespiratory disease, daily cardiovascular activity and imaging
Twin studies have helped gain insight into the role of heritability in disease and disease processes. Given the large burden cardiorespiratory diseases place on society, these diseases have featured largely in twin studies. In part A of this chapter, a brief overview of the outcomes of such studies is provided for a wide variety of cardiovascular and respiratory diseases. A moderate to high influence of genes is seen for the vast majority of these diseases. This highlights the importance of screening high-risk individuals, as well as studying gene-by-environment interactions. While studying the disease itself is important, insight into the processes leading up to the disease may increase our understanding of disease development. By studying cardiovascular function for prolonged periods of time in nonpatient populations, valuable insights can be obtained in normal day cardiovascular functioning. In part B of this chapter, we review twin studies in which indices of cardiovascular function were recorded throughout the day and night using ambulatory monitoring. Here too, it is evident that heritability influences the variation of everyday blood pressure and heart action. Another way of gaining insight into the physiological processes underlying disease development is through imaging studies. In part C of this chapter, we discuss the inclusion of twins in imaging studies. Twin studies of imaging data are still sparse and cover a wide variety of traits. Studies including both monozygotic and dizygotic twins generally point to a role for genetic factors, though the degree differs across the traits. Within imaging studies, the twin discordant design is also often applied, demonstrating the occurrence of gene-by-environment interaction. Overall, twin studies have shown that genetic factors play an important role in individual variation in many physiological diseases and disease processes. Future studies are expected to provide more insight into the interplay of genetic and environmental factors with respect to physiological function and risk. Of particular interest are studies looking into epigenetic mechanisms, which are gradually emerging and may further help the development of more personalized medicine, based on genetic vulnerability as well as lifestyle and environment
Are the Morphological Indices of the Vertebrobasilar System Heritable? A Twin Study Based on 3D Reconstructed Models
Background and Objectives: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited. Materials and Methods: We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects. Results: 39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7–75.2%; E: 37%; 95% CI: 24.8–54.3%) and volume (A: 60.1%; 95% CI: 42.4–73.2%; E: 39.9%; 95% CI: 26.8–57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment. Conclusions: The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system
Lobular Difference in Heritability of Brain Atrophy among Elderly Japanese: A Twin Study
Background and Objectives: Brain atrophy is related to cognitive decline. However, the heritability of brain atrophy has not been fully investigated in the Eastern Asian population. Materials and Methods: Brain imaging of 74 Japanese twins registered in the Osaka University Twin Registry was conducted with voxel-based morphometry SPM12 and was processed by individual voxel-based morphometry adjusting covariates (iVAC) toolbox. The atrophy of the measured lobes was obtained by comparing the focal volume to the average of healthy subjects. Classical twin analysis was used to measure the heritability of its z-scores. Results: The heritability of brain atrophy ranged from 0.23 to 0.97, depending upon the lobes. When adjusted to age, high heritability was reported in the frontal, frontal-temporal, and parietal lobes, but the heritability in other lobes was lower than 0.70. Conclusions: This study revealed a relatively lower heritability in brain atrophy compared to other ethnicities. This result suggests a significant environmental impact on the susceptibility of brain atrophy the Japanese. Therefore, environmental factors may have more influence on the Japanese than in other populations
Genetic influence on femoral plaque and its relationship with carotid plaque: an international twin study.
To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis
Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification
Background and objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries’ atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37–1] and 0.69 [95% CI: 0.38–1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0–0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30–0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42–1]. Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization
Genetic influences on the onset of obstructive sleep apnoea and daytime sleepiness: a twin study
Background
Obstructive sleep apnoea (OSA) is one of the major sources of the excessive daily sleepiness, cognitive dysfunction, and it increases cardiovascular morbidity and mortality. Previous studies suggested a possible genetic influence, based on questionnaires but no objective genetic study was conducted to understand the exact variance underpinned by genetic factors.
Methods
Seventy-one Hungarian twin pairs involved from the Hungarian Twin Registry (48 monozygotic, MZ and 23 dizygotic, DZ pairs, mean age 51 ± 15 years) underwent overnight polysomnography (Somnoscreen Plus Tele PSG, Somnomedics GMBH, Germany). Apnoea hypopnea index (AHI), respiratory disturbance index (RDI) and oxygen desaturation index (ODI) were registered. Daytime sleepiness was measured with the Epworth Sleepiness Scale (ESS). Bivariate heritability analysis was applied.
Results
The prevalence of OSA was 41% in our study population. The heritability of the AHI, ODI and RDI ranged between 69% and 83%, while the OSA, defined by an AHI ≥5/h, was itself 73% heritable. The unshared environmental component explained the rest of the variance between 17% and 31%. Daytime sleepiness was mostly determined by the environment, and the variance was influenced in 34% by the additive genetic factors. These associations were present after additional adjustment for body mass index.
Conclusion
OSA and the indices of OSA severity are heritable, while daytime sleepiness is mostly influenced by environmental factors. Further studies should elucidate whether close relatives of patients with OSA may benefit from early family risk based screening.This study was supported by the Hungarian Pulmonology Foundation of the Hungarian Society of Pulmonologists (2014, TDL) and Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (AB)
Circulating levels of clusterin and complement factor H in patients with obstructive sleep apnea
Aim: Obstructive sleep apnea (OSA) activates the complement system; however, the levels of membrane attack complex (MAC) are unaltered suggesting regulatory mechanisms. Our aim was to investigate complement factor H (CFH) and clusterin, two important complement regulators in OSA. Materials & methods: We analyzed clusterin and CFH levels in plasma of 86 patients with OSA and 33 control subjects. Results: There was no difference in CFH levels between patients (1099.4/784.6–1570.5/μg/ml) and controls (1051.4/652.0–1615.1/μg/ml, p = 0.72). Clusterin levels were higher in patients with OSA (309.7/217.2–763.2/μg/ml vs 276.1/131.0–424.3/μg/ml, p = 0.048) with a trend for a positive correlation with disease severity (p = 0.073). Conclusion: Increase in clusterin levels may be protective in OSA by blocking the MAC formation
The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
Kaprio, Jaakko/0000-0002-3716-2455; Knafo-Noam, Ariel/0000-0003-0613-1960; de Freitas, Duarte Luis/0000-0001-6642-3370; Haworth, Claire/0000-0002-8608-289X; Siribaddana, Sisira/0000-0001-5821-2557; Kyvik, Kirsten O/0000-0003-2981-0245; Aliev, Fazil/0000-0001-8357-4699; Craig, Jeffrey M/0000-0003-3979-7849; Ordonana, Juan R./0000-0001-7779-6017; Sund, Reijo/0000-0002-6268-8117; Bartels, Meike/0000-0002-9667-7555; Kandler, Christian/0000-0002-9175-235X; Fagnani, Corrado/0000-0001-5771-7772; Huibregtse, Brooke M./0000-0003-0977-7249; Montgomery, Grant W/0000-0002-4140-8139; Colodro-Conde, Lucia/0000-0002-9004-364X; Loos, Ruth J F/0000-0002-8532-5087; Busjahn, Andreas/0000-0001-9650-6919; ONCEL, Sevgi YURT/0000-0002-0990-292X; Christensen, Kaare/0000-0002-5429-5292; Martin, Nicholas/0000-0003-4069-8020; Tan, Qihua/0000-0003-3194-0030; ROMERA, JUAN FRANCISCO SANCHEZ/0000-0002-5405-6216; D'Ippolito, Cristina/0000-0001-7902-9380; Skytthe, Axel E/0000-0002-8629-4913; Tan, Qihua/0000-0003-3194-0030; Heikkila, Kauko/0000-0002-9256-8028; Duncan, Glen/0000-0001-6909-1869; Jelenkovic, Aline/0000-0002-6191-8371; Magnusson, Patrik/0000-0002-7315-7899; mangino, massimo/0000-0002-2167-7470; Medland, Sarah E/0000-0003-1382-380X; Saffery, Richard/0000-0002-9510-4181; Plomin, Robert/0000-0002-0756-3629; Harden, Kathryn/0000-0002-1557-6737; Hotopf, Matthew/0000-0002-3980-4466; McAdams, Tom/0000-0002-6825-3499; Aaltonen, Sari/0000-0002-2873-4263; Kremen, William/0000-0002-8629-5609; Pahlen, Shandell/0000-0003-0753-4155; Llewellyn, Clare/0000-0002-0066-2827; Franz, Carol/0000-0002-8987-1755; Derom, Catherine/0000-0001-5574-796X; Willemsen, Gonneke/0000-0003-3755-0236; Rasmussen, Finn/0000-0001-7915-7809; Rebato, Esther/0000-0003-1221-8501; lee, kayoung/0000-0002-2816-554X; Sodemann, Morten/0000-0001-8992-2500; Gatz, Margaret/0000-0002-1071-9970; Boivin, Michel/0000-0001-8621-9844; Silventoinen, Karri/0000-0003-1759-3079For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m(2)) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1RO1-AG13662-01A2]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AG039572]; WT Grant Foundation; University of London Central Research fund; Medical Research CouncilMedical Research Council UK (MRC) [G81/343, G120/635]; Economic and Social Research CouncilEconomic & Social Research Council (ESRC) [RES-000-22-2206]; Institute of Social Psychiatry [06/07-11]; Leverhulme Research FellowshipLeverhulme Trust [RF/2/RFG/2008/0145]; Goldsmiths; University of London; National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1B00047]; Danish Agency for Science, Technology and Innovation; Research Council for Health and Disease; Velux Foundation; US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 AG08761]; Fund of Scientific Research, FlandersFWO; Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium); Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study [HD10333]; National Institute of Health grantsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; Cooperative Studies Program of the Office of Research AMP; Development of the United States Department of Veterans Affairs; Centre of Research Excellence from the National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; Michigan State University from the National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; The National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01ESO15150-01]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81125007]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [437015, 607358]; Bonnie Babes Foundation [BBF20704]; Financial Markets Foundation for Children [032-2007]; Victorian Government's Operational Infrastructure Support Program; ENGAGE-European Network for Genetic and Genomic Epidemiology [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 264146]; Osaka University's International Joint Research Promotion Program; Kirikkale University Research Grant: KKUKirikkale University; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; European Research Council (ERC)European Research Council (ERC) [240994]; European Union's Seventh Framework Programmes ENGAGE ConsortiumEuropean Union (EU) [HEALTH-F4-2007-201413]; BioSHaRE EU [HEALTH-F4-2010-261433]; Seneca FoundationFundacion Seneca; Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10]; Ministry of Science and Innovation, SpainSpanish Government [PSI11560-2009]; UK Medical Research CouncilMedical Research Council UK (MRC) [G0901245]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [31/D19086]; Portuguese agency for research (The Foundation for Science and Technology) [POCI/DES/56834/2004]; National Institutes of Health.United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375]; Wellcome TrustWellcome Trust; European Community's Seventh Framework ProgrammeEuropean Union (EU); National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London; Netherlands Organization for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; VU University's Institute for Health and Care Research (EMGO+); European Research CouncilEuropean Research Council (ERC) [ERC-230374]; Avera Institute, Sioux Falls, South Dakota (USA); Cancer Research UKCancer Research UK [C1418/A7974]; [5T32DA017637-10]; [NIH RC2 HL103416]; Cancer Research UKCancer Research UK [14133]; Medical Research CouncilMedical Research Council UK (MRC) [G0901245, MC_UU_12013/1]; NNF Center for Basic Metabolic ResearchNovo Nordisk Foundation [Metabolic Genetics]; Novo Nordisk FondenNovo NordiskNovo Nordisk Foundation [NNF10CC1016515]This study was conducted within the CODATwins project (Academy of Finland #266592). Support for participating twin projects: the University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Waves 1-3 of Genesis 12-19 were funded by the WT Grant Foundation, the University of London Central Research fund and a Medical Research Council Training Fellowship (G81/343) and Career Development Award (G120/635) to Thalia C. Eley. Wave 4 was supported by grants from the Economic and Social Research Council (RES-000-22-2206) and the Institute of Social Psychiatry (06/07-11) to Alice M. Gregory who was also supported at that time by a Leverhulme Research Fellowship (RF/2/RFG/2008/0145). Wave 5 was supported by funding to Alice M. Gregory from Goldsmiths, University of London. Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1B00047). The Danish Twin Registry is supported by the National Program for Research Infrastructure 2007 from the Danish Agency for Science, Technology and Innovation, The Research Council for Health and Disease, the Velux Foundation and the US National Institute of Health (P01 AG08761). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). The Colorado Twin Registry is funded by NIDA funded center grant DA011015 and Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637-10. The Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The Australian Twin Registry is supported by a Centre of Research Excellence (grant ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health.; r The California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Guangzhou Twin Eye Study is supported by National Natural Science Foundation of China (grant #81125007). PETS was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to JC, and RS), the Bonnie Babes Foundation (grant number BBF20704 to JMC), the Financial Markets Foundation for Children (grant no. 032-2007 to JMC), and by the Victorian Government's Operational Infrastructure Support Program. Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R. J. Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J. Kaprio). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. S. Y. Oncel and F. Aliev are supported by Kirikkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. The Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. Data collection and research stemming from the Norwegian Twin Registry is supported, in part, from the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413, and BioSHaRE EU (grant agreement HEALTH-F4-2010-261433). The Murcia Twin Registry is supported by the Seneca Foundation, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08 & 15302/PHCS/10) and Ministry of Science and Innovation, Spain (PSI11560-2009). The Twins Early Development Study (TEDS) is supported by a program grant (G0901245) from the UK Medical Research Council and the work on obesity in TEDS is supported in part by a grant from the UK Biotechnology and Biological Sciences Research Council (31/D19086). The Madeira data comes from the following project: genetic and environmental influences on physical activity, fitness, and health: the Madeira family study Project reference: POCI/DES/56834/2004 founded by the Portuguese agency for research (The Foundation for Science and Technology). The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The University of Washington Twin Registry is supported by the grant NIH RC2 HL103416 (D. Buchwald, PI). The Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC-230374), the Avera Institute, Sioux Falls, South Dakota (USA).; r Gemini was supported by a grant from Cancer Research UK (C1418/A7974)
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