Browsing by Subject "Twin study"

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  • Bogl, Leonie H.; Kaye, Sanna M.; Ramo, Joel T.; Kangas, Antti J.; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietilainen, Kirsi H. (2016)
    Objective. To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Subjects and methods. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (r(g)) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference >= 3 kg/m(2)). Results. Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (r(g) = 0.40), glycoprotein (r(g) = 0.37), serum triglycerides (r(g) = 0.36), BCAAs (r(g) = 0.30-0.40), HDL particle diameter (r(g) = -0.33) and HDL cholesterol (r(g) = -0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. Conclusions. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. (C) 2015 Elsevier Inc. All rights reserved.
  • Tuomela, Jenni; Kaprio, Jaakko; Sipilä, Pyry N.; Silventoinen, Karri; Wang, Xin; Ollikainen, Miina; Piirtola, Maarit (2019)
    Objective: To determine the accuracy of self-reported height, weight, body mass index (BMI) and waist circumference (WC) compared to the measured values, and to assess the similarity between self-reported and measured values within dizygotic (DZ) and monozygotic (MZ) twin pairs. Methods: The data on self-reported and measured height, weight and WC values as well as measured hip circumference (HC) were collected from 444 twin individuals (53-67 years old, 60% women). Accuracies between self-reported and measured values were assessed by Pearson's correlation coefficients, Cohen's kappa coefficients and Bland-Altman 95% limits of agreement. Intra-class correlation was used in within-pair analyses. Results: The correlations between self-reported and measured values were high for all variables (r = 0.86-0.98), although the agreement assessed by Bland-Altman 95% limits had relatively wide variation. The degree of overestimating height was similar in both sexes, whereas women tended to underestimate and men overestimate their weight. Cohen's kappa coefficients between self-reported and measured BMI categories were high: 0.71 in men and 0.70 in women. Further, the mean self-reported WC was less than the mean measured WC (difference in men 2.5 cm and women 2.6 cm). The within-pair correlations indicated a tendency of MZ co-twins to report anthropometric measures more similarly than DZ co-twins. Conclusions: Self-reported anthropometric measures are reasonably accurate indicators for obesity in large cohort studies. However, the possibility of more similar reporting among MZ pairs should be taken into account in twin studies exploring the heritability of different phenotypes. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of Asia Oceania Association for the Study of Obesity.
  • Sillanpää, Elina; Heikkinen, Aino; Kankaanpää, Anna; Paavilainen, Aini; Kujala, Urho M.; Tammelin, Tuija H.; Kovanen, Vuokko; Sipilä, Sarianna; Pietiläinen, Kirsi H.; Kaprio, Jaakko; Ollikainen, Miina; Laakkonen, Eija K. (BioMed Central, 2021)
    Abstract The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.
  • Linna, Milla S.; Kaprio, Jaakko; Raevuori, Anu; Sihvola, Elina; Keski-Rahkonen, Anna; Rissanen, Aila (2013)
  • Zyla, Joanna; Kabacik, Sylwia; O'Brien, Grainne; Wakil, Salma; Al-Harbi, Najla; Kaprio, Jaakko; Badie, Christophe; Polanska, Joanna; Alsbeih, Ghazi (2019)
    Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment. A comprehensive analysis of genome-wide single-nucleotide polymorphisms (SNPs) and a transcriptional response to ionising radiation exposure in twins have the potential to identify such an individual. In the present work, we investigated SNP profile and CDKN1A gene expression in blood T lymphocytes from 130 healthy Caucasians with a complex level of individual kinship (unrelated, mono- or dizygotic twins). It was found that genetic variation accounts for 66% (95% CI 37-82%) of CDKN1A transcriptional response to radiation exposure. We developed a novel integrative multi-kinship strategy allowing investigating the role of genome-wide polymorphisms in transcriptomic radiation response, and it revealed that rs205543 (ETV6 gene), rs2287505 and rs1263612 (KLF7 gene) are significantly associated with CDKN1A expression level. The functional analysis revealed that rs6974232 (RPA3 gene), involved in mismatch repair (p value = 9.68e-04) as well as in RNA repair (p value = 1.4e-03) might have an important role in that process. Two missense polymorphisms with possible deleterious effect in humans were identified: rs1133833 (AKIP1 gene) and rs17362588 (CCDC141 gene). In summary, the data presented here support the validity of this novel integrative data analysis strategy to provide insights into the identification of SNPs potentially influencing radiation sensitivity. Further investigations in radiation response research at the genomic level should be therefore continued to confirm these findings.
  • Bogl, Leonie H.; Kaprio, Jaakko; Pietiläinen, Kirsi H. (2020)
    Background & aim: Lifestyle changes focusing on diet and exercise remain the cornerstone of the treatment of non-alcoholic fatty liver disease (NAFLD). The present co-twin control study of monozygotic (MZ) twin pairs was designed to identify nutritional factors potentially involved in the pathogenesis of NAFLD. Methods: Cross-sectional study of 50 MZ twin pairs (age range: 23-36 years), of which ten pairs were discordant for liver fat (liver fat percentage of one twin 5% and a difference between co-twins of >5%) as determined by magnetic resonance spectroscopy. Nutrient intake was calculated from 3-day food records. Results: Among the ten liver fat-discordant twin pairs, the n-6: n-3 ratio was significantly higher in the twins with higher liver as compared to their co-twins with lower liver fat (6.6:1 vs. 3.2:1, p-value = 0.005). In multiple regression analysis of within-pair differences including all 50 twin pairs, a higher n-6: n-3 ratio was significantly associated with a higher liver fat percentage within MZ twin pairs after adjustment for body mass index, energy intake and other covariates (standardized beta = 0.43, p-value = 0.001). Conclusions: Our findings suggest that the n-6: n-3 ratio is a promising dietary agent for the prevention and treatment of NAFLD. Clinical trials are required to better understand causal relationships and required doses. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
  • Sillanpaa, Elina; Tormakangas, Timo; Rantanen, Taina; Kaprio, Jaakko; Sipila, Sarianna (2016)
    Leukocyte telomere length (LTL) is known to be associated with mortality, but its association with age-related decline in physical functioning and the development of disability is less clear. This study examined the associations between LTL and physical functioning, and investigated whether LTL predicts level of physical functioning over an 11-year follow-up. Older mono-(MZ) and dizygotic (DZ) twin sisters (n = 386) participated in the study. Relative LTL was measured by qPCR at baseline. Physical functioning was measured by 6-min walking distance and level of physical activity (PA). Walking distance was measured at baseline and at 3-year follow-up. PA was assessed by questionnaire at baseline and at 3- and 11-year follow-ups. The baseline analysis was performed with path models, adjusted with age and within-pair dependence of twin pairs. The longitudinal analysis was performed with a repeated measures linear model adjusted for age and longitudinal within-pair dependence. A nonrandom missing data analysis was utilized. At baseline, in all individuals, LTL was associated with PA (est. 0.14, SE 0.06, p = 0.011), but not with walking distance. Over the follow-up, a borderline significant association was observed between LTL and walking distance (est. 0.14, SE 0.07, p = 0.060) and a significant association between LTL and PA (est. 0.19, SE 0.06, p = 0.001). The results suggest that LTL is associated with PA and may, therefore, serve as a biomarker predicting the development of disability. Longitudinal associations between LTL and PA were observed only when nonrandom data missingness was taken into account in the analysis.
  • Huang, Yisong; Ollikainen, Miina; Muniandy, Maheswary; Zhang, Tao; van Dongen, Jenny; Hao, Guang; van Der Most, Peter J.; Pan, Yue; Pervjakova, Natalia; Sun, Yan; Hui, Qin; Lahti, Jari; Fraszczyk, Eliza; Lu, Xueling; Sun, Dianjianyi; Richard, Melissa A.; Willemsen, Gonneke; Heikkila, Kauko; Leach, Irene Mateo; Mononen, Nina; Kähönen, Mika; Hurme, Mikko A.; Raitakari, Olli T.; Drake, Amanda J.; Perola, Markus; Nuotio, Marja-Liisa; Huang, Yunfeng; Khulan, Batbayar; Räikkönen, Katri; Wolffenbuttel, Bruce H. R.; Zhernakova, Alexandra; Fu, Jingyuan; Zhu, Haidong; Dong, Yanbin; van Vliet-Ostaptchouk, Jana V.; Franke, Lude; Eriksson, Johan G.; Fornage, Myriam; Milani, Lili; Lehtimäki, Terho; Vaccarino, Viola; Boomsma, Dorret; van Der Harst, Pim; de Geus, Eco J. C.; Salomaa, Veikko; Li, Shengxu; Chen, Wei; Su, Shaoyong; Wilson, James; Snieder, Harold; Kaprio, Jaakko; Wang, Xiaoling (2020)
    We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites withP
  • Kaartinen, Sara; Aaltonen, Sari; Korhonen, Tellervo; Latvala, Antti; Mikkelsson, Marja; Kujala, Urho M.; Kaprio, Jaakko (2019)
    This study investigates cross-sectional and longitudinal associations between the diversity of leisure-time sport activities and the frequencies of low back pain (LBP) and neck-shoulder region pain (NSP) in twins, including a cross-sectional within-pair design to adjust for potential familial confounding. Finnish twins born in 1975–79 (FinnTwin16 study) reported participation in leisure-time sport activities at the mean ages of 17 (1992–96) (n = 5096, 54% females) and 34 years (2010−12) (n = 3731, 57% females). Diversity assessed as the number of sport activities was categorized as 1, 2, 3, 4, and ≥ 5, excluding inactive individuals. The frequencies of LBP (n = 3201) and NSP (n = 3207), reported at age 34, were categorized as never/seldom, monthly, or weekly pain. Cross-sectional and longitudinal individual-based associations between the number of sport activities and the frequency of LBP and NSP were investigated with multinomial logistic regression analyses, adjusting for multiple confounders. Cross-sectionally, participation in ≥5 sport activities, compared to 1 sport, was associated with significantly less weekly LBP (OR = 0.63, 95%CI = 0.43–0.90), but not with NSP. Longitudinally, participation in several sport activities in adolescence had no significant association with LBP or NSP in adulthood. Cross-sectional within-pair analyses were conducted among twin pairs discordant for LBP (n = 507) and NSP (n = 579). The associations between monozygotic and dizygotic twin pairs were similar in LBP-discordant pairs but differed within NSP-discordant pairs. Participation in ≥5 sport activities in adulthood may be associated with less weekly LBP, but not with monthly LBP or the frequency of NSP. However, within-pair analyses for NSP suggest confounding due to shared familial factors.
  • Seesjärvi, Erik (Helsingin yliopisto, 2014)
    The aim of the study was to estimate the proportional effects of genetic and environmental factors on individual differences in music perception. Previous research has demonstrated that genetic effects explain a substantial amount of these differences, and that common environmental effects have been low or have not been examined because of methodological constraints. However, in defining the accuracy of music perceptual skills, most previous studies have used somewhat simple auditory stimuli this choice limiting their generalizability. In order to reliably determine the proportional effects of genetic and environmental factors on perception of more complex musical stimuli, the present study utilized unfamiliar melodies, the classical twin design, and structural equation modelling. The participants of the current study were 384 twins from the longitudinal FinnTwin16 study, aged 32–38 years. They performed an online music perception test that consists of two subtests with pitch-related tasks (Scale and Out-of-key subtests) and one subtest with a time-related task (Off-beat subtest). The test includes 30 unfamiliar melodies. The participants also answered a short questionnaire regarding their educational background and self-assessed musical ability. The results showed that genetic factors explained about half of the interindividual variance in ability to detect pitch changes in repeated melodies (Scale subtest), whereas common environmental factors had only marginal effect on this ability. Furthermore, genetic factors explained about a quarter or less of the interindividual variance in ability to detect a timing delay that was disrupting the meter or rhythm of melody (Off-beat subtest). There were no common environmental effects. In contrast, a different pattern of results was obtained for ability to detect a tone that violated the established scale expectations (Out-of-key subtest) in which there were only marginal genetic effects whereas common environmental factors explained over half of the interindividual variance. Together with the previous research, these results show that genetic factors explain a significant portion of the individual differences in music perception tasks especially when the task is sufficiently demanding cognitively. However, when the task demands explicit or implicit knowledge of musical scales, genetic effects disappear and the individual differences can mostly be explained by common environmental factors.
  • Jukarainen, Sakari; Heinonen, Sini; Rämö, Joel; Rinnankoski-Tuikka, Rita; Rappou, Elisabeth; Tummers, Mark; Muniandy, Maheswary; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Kaprio, Jaakko; Rissanen, Aila; Pirinen, Eija; Pietiläinen, Kirsi (Helsingfors universitet, 2016)
    Context: Sirtuins (SIRTs) regulate cellular metabolism and mitochondrial function according to the energy state of the cell reflected by NAD+‚ levels. Objective: Our aim was to determine whether expressions of SIRTs and NAD+‚ biosynthesis genes are affected by acquired obesity and how possible alterations are connected with metabolic dys-function while controlling for genetic and familial factors. Design and Participants: We studied a cross-sectional sample of 40 healthy pairs of monozygotic twins, including 26 pairs who were discordant for body mass index (within-pair difference +ƒ 3 kg/m2), from the FinnTwin12 and FinnTwin16 cohorts. Main Outcome Measures: Subcutaneous adipose tissue (SAT) transcriptomics was analyzed by using Affymetrix U133 Plus 2.0 chips, total SAT (poly-ADP) ribose polymerase (PARP) activity by an ELISA kit, body composition by dual-energy x-ray absorptiometry and magnetic resonance imaging/spectroscopy, and insulin sensitivity by an oral glucose tolerance test. Results: SIRT1, SIRT3, SIRT5, NAMPT, NMNAT2, NMNAT3, and NRK1 expressions were significantly down-regulated and the activity of main cellular NAD+‚ consumers, PARPs, trended to be higher in the SAT of heavier cotwins of body mass index–discordant pairs. Controlling for twin-shared factors, SIRT1, SIRT3, NAMPT, NMNAT3, and NRK1 were significantly negatively correlated with adiposity, SIRT1, SIRT5, NMNAT2, NMNAT3, and NRK1 were negatively correlated with inflammation, and SIRT1 and SIRT5 were positively correlated with insulin sensitivity. Expressions of genes involved in mitochondrial unfolded protein response were also significantly down-regulated in the heavier cotwins. Conclusions: Our data highlight a strong relationship of reduced NAD+‚/SIRT pathway expression with acquired obesity, inflammation, insulin resistance, and impaired mitochondrial protein homeostasis in SAT.
  • Ranjit, Anu; Buchwald, Jadwiga; Latvala, Antti; Heikkila, Kauko; Tuulio-Henriksson, Annamari; Rose, Richard J.; Kaprio, Jaakko; Korhonen, Tellervo (2019)
    Longitudinal, genetically informative studies of the association between cigarette smoking and depressive symptoms among adolescents are limited. We examined the longitudinal association of cigarette smoking with subsequent depressive symptoms during adolescence in a Finnish twin cohort. We used prospective data from the population-based FinnTwin12 study (maximum N = 4152 individuals, 1910 twin pairs). Current smoking status and a number of lifetime cigarettes smoked were assessed at the age of 14 and depressive symptoms at the age of 17. Negative binomial regression was conducted to model the association between smoking behavior and subsequent depressive symptoms among individuals, and within-pair analyses were conducted to control for unmeasured familial confounding. Analyses were adjusted for age, sex, school grades, drinking alcohol to intoxication, health status, family structure, parental education, and smoking, as well as for pre-existing depressiveness. The results of the individual-level analyses showed that cigarette smoking at the age of 14 predicted depressive symptoms at the age of 17. Compared to never smokers, those who had smoked over 50 cigarettes (incidence rate ratio, IRR = 1.43, 95% CI 1.28-1.60) and regular smokers (IRR = 1.46, 95% CI 1.32-1.62) had higher depression scores. The associations were attenuated when adjusted for measured covariates and further reduced in within-pair analyses. In the within-pair results, the estimates were lower within monozygotic (MZ) pairs compared to dizygotic (DZ) pairs, suggesting that shared genetic factors contribute to the associations observed in individual-based analyses. Thus, we conclude that cigarette smoking is associated with subsequent depressive symptoms during adolescence, but the association is not independent of measured confounding factors and shared genetic influences.