Browsing by Subject "twins"

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  • Kahila, Hanna; Marjonen, Heidi; Auvinen, Pauliina; Avela, Kristiina; Riikonen, Raili; Kaminen-Ahola, Nina (2020)
    Abstract Background A pair of dizygotic twins discordantly affected by heavy prenatal alcohol exposure (PAE) was reported previously by Riikonen, suggesting the role of genetic risk or protective factors in the etiology of alcohol-induced developmental disorders. Now, we have re-examined these 25-year-old twins and explored genetic origin of the phenotypic discordancy reminiscent with fetal alcohol syndrome (FAS). Furthermore, we explored alterations in DNA methylation profile of imprinting control region at growth-related insulin-like growth factor 2 (IGF2)/H19 locus in twins' white blood cells (WBC), which have been associated earlier with alcohol-induced genotype-specific changes in placental tissue. Methods Microarray-based comparative genomic hybridization (aCGH) was used to detect potential submicroscopic chromosomal abnormalities, and developmental as well as phenotypic information about twins were collected. Traditional bisulfite sequencing was used for DNA methylation analysis. Results Microarray-based comparative genomic hybridization revealed a microdeletion 18q12.3-q21.1. in affected twin, residing in a known 18q deletion syndrome region. This syndrome has been associated with growth restriction, developmental delay or intellectual deficiency, and abnormal facial features in previous studies, and thus likely explains the phenotypic discordancy between the twins. We did not observe association between WBCs? DNA methylation profile and PAE, but interestingly, a trend of decreased DNA methylation at the imprinting control region was seen in the twin with prenatal growth retardation at birth. Conclusions The microdeletion emphasizes the importance of adequate chromosomal testing in examining the etiology of complex alcohol-induced developmental disorders. Furthermore, the genotype-specific decreased DNA methylation at the IGF2/H19 locus cannot be considered as a biological mark for PAE in adult WBCs.
  • Jelenkovic, Aline; Yokoyama, Yoshie; Sund, Reijo; Pietilainen, Kirsi H.; Hur, Yoon-Mi; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Toos C. E. M.; Ooki, Syuichi; Saudino, Kimberly J.; Stazi, Maria A.; Fagnani, Corrado; D'Ippolito, Cristina; Nelson, Tracy L.; Whitfield, Keith E.; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Heikkila, Kauko; Cutler, Tessa L.; Hopper, John L.; Wardle, Jane; Llewellyn, Clare H.; Fisher, Abigail; Corley, Robin P.; Huibregtse, Brooke M.; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D.; LTarnoki, David; Burt, S. Alexandra; Klump, Kelly L.; Ordonana, Juan R.; Sanchez-Romera, Juan F.; Colodro-Conde, Lucia; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Harris, Jennifer R.; Brandt, Lngunn; Nilsen, Thomas Sevenius; Craig, Jeffrey M.; Saffery, Richard; Rasmussen, Finn; Tynelius, Per; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Haworth, Claire M. A.; Plomin, Robert; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Krueger, Robert F.; Mcgue, Matt; Pahlen, Shandell; Boomsma, Dorret I.; Sorensen, Thorkild I. A.; Kaprio, Jaakko; Silventoinen, Karri (2017)
    Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m(2) higher BMI (P <0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m(2) per kg birthweight, P <0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood.
  • Lindgren, Noora; Tuisku, Jouni; Vuoksimaa, Eero; Helin, Semi; Karrasch, Mira; Marjamäki, Päivi; Kaprio, Jaakko; Rinne, Juha O. (2020)
    Alzheimer's disease is associated with chronic response of innate immune system, referred as neuroinflammation. PET radioligands binding to the 18kDa translocator protein are potential biomarkers of neuroinflammation. Translocator protein PET studies in mild cognitive impairment and Alzheimer's disease have indicated controversial results, possibly reflecting interindividual variation and heterogeneity of study populations. We controlled for genetic and environmental effects by studying twin pairs discordant for episodic memory performance. Episodic memory impairment is a well-known cognitive hallmark of early Alzheimer's disease process. Eleven same-sex twin pairs (four monozygotic pairs, six female pairs, age 72-77 years) underwent [C-11]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine ([C-11]PBR28) PET imaging, structural magnetic resonance imaging and neuropsychological testing in 2014-17. Main PET outcome was the volume-weighted average standardized uptake value of cortical regions vulnerable to Alzheimer's disease pathology. Ten pairs were discordant for episodic memory performance. In the eight pairs with identical translocator protein genotype, twins with poorer episodic memory had similar to 20% higher cortical [C-11]PBR28 binding compared with their better-performing co-twins (mean intra-pair difference 0.21 standardized uptake value, 95% confidence interval 0.05-0.37, P = 0.017). The result remained the same when including all discordant pairs and controlling for translocator protein genotype. Increased translocator protein PET signal suggests that increased microglial activation is associated with poorer episodic memory performance. Twins with worse episodic memory performance compared with their co-twins had on average 20% higher uptake of the neuroinflammatory marker translocator protein PET tracer (11)[C-11]PBR28. The findings support a negative association between neuroinflammation and episodic memory and the use of translocator protein positron emission tomography as a useful indicator of Alzheimer's disease process.
  • Piirtola, Maarit; Kaprio, Jaakko; Svedberg, Pia; Silventoinen, Karri; Ropponen, Annina (2020)
  • Virtanen, Suvi; Kaprio, Jaakko; Viken, Richard; Rose, Richard J.; Latvala, Antti (2019)
    Aims To estimate birth cohort effects on alcohol consumption and abstinence in Finland and to test differences between birth cohorts in genetic and environmental sources of variation in Finnish adult alcohol use. Design The Older Finnish Twin Cohort longitudinal survey study 1975-2011. Setting Finland. Participants A total of 26 121 same-sex twins aged 18-95 years (full twin pairs at baseline n = 11 608). Measurements Outcome variables were the quantity of alcohol consumption (g/month) and abstinence (drinking zero g/month). Predictor variables were 10-year birth cohort categories and socio-demographic covariates. In quantitative genetic models, two larger cohorts (born 1901-20 and 1945-57) were compared. Findings Multi-level models in both sexes indicated higher levels of alcohol consumption in more recent birth cohorts and lower levels in earlier cohorts, compared with twins born 1921-30 (all P < 0.003). Similarly, compared with twins born 1921-30, abstaining was more common in earlier and less common in more recent cohorts (all P < 0.05), with the exception of men born 1911-20. Birth cohort differences in the genetic and environmental variance components in alcohol consumption were found: heritability was 21% [95% confidence interval (CI) = 0-56%] in the earlier-born cohort of women [mean age 62.8, standard deviation (SD) = 5.3] and 51% (95% CI = 36-56%) in a more recent cohort (mean age 60.2, SD = 3.7) at the age of 54-74. For men, heritability was 39% (95% CI = 27-45%) in both cohorts. In alcohol abstinence, environmental influences shared between co-twins explained a large proportion of variation in the earlier-born cohort (43%, 95% CI = 23-63%), whereas non-shared environmental (54%, 95% CI = 39-72%) and additive genetic influences (40%, 95% CI = 13-61%) were more important among more recent cohorts of men and women. Conclusion The contribution of genetic and environmental variability to variability in alcohol consumption in the Finnish population appears to vary by birth cohort.
  • Tapola, Lauri (Helsingfors universitet, 2008)
    The temperamental traits of Cloninger's personality theory (novelty seeking, harm avoidance, reward dependence and persistence) reflect independent systems of central nervous system deciding responses toward new, rewarding and aversive stimuli. Thus, certain temperamental traits and their combinations may predispose to heavy drinking and alcohol dependence. Hence, the aim of the present study was to investigate associations between temperamental traits and the amount of alcohol consumption, frequency of heavy drinking and the maximum number of drinks per occasion. In this study, we investigated also whether these associations are only confounded by between-family differences in genetic and environmental factors. Furthermore the associations between temperamental trait combinations that reflect Cloninger's typology of alcoholism and alcohol use were studied. The subjects (n=401) in the current study were a group of FinnTwin16 study participators, Finnish twins born in 1974-79. Temperament was measured with TCI-R (Temperament and Character Inventory-Revised) a self-report form. The amount of alcohol consumption was asked by Semi-structured interview (Semi-Structured Assessment of Genetics of Alcoholism = SSAGA). The frequency of heavy drinking and maximum number of drinks per occasion were asked by mail form. In accordance with previous studies, novelty seeking had a positive relationship with the amount of alcohol consumption, frequency of heavy drinking and the maximum number of drinks per occasion in both genders. In this study, the association was proven independent of between-family differences in genetic and environmental factors that are associated to both novelty seeking and alcohol use. Surprisingly, reward dependence was negatively related to the maximum number of drinks per occasion in both genders. Persistence had a weak positive relationship with maximum number of drinks per occasion in men. The temperamental trait combinations that reflect Cloninger's typology of alcoholism did not differ from the other combinations in regard to alcohol use as hypothesized. The results confirm the previous finding about the relationship between novelty seeking and alcohol use. Support for Cloninger's typology of alcoholism in regard to combinations of temperamental trait was not achieved in this study.
  • Virtanen, Suvi; Kuja-Halkola, Ralf; Mataix-Cols, David; Jayaram-Lindström, Nitya; D'Onofrio, Brian M.; Larsson, Henrik; Ruck, Christian; Suvisaari, Jaana; Lichtenstein, Paul; Latvala, Antti (2020)
    Background Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors. Methods We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis. Results Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse. Conclusions Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.
  • Ahlberg, Jari; Piirtola, Maarit; Lobbezoo, Frank; Manfredini, Daniele; Korhonen, Tellervo; Aarab, Ghizlane; Hublin, Christer; Kaprio, Jaakko (2020)
    Background Sleep bruxism (SB) and awake bruxism (AB) have been considered different entities, although co-occurrence between them has been shown. While genetic factors have a marked influence on phenotypic variance in liability to SB, this remains unclear for AB. Aim To examine the degree of co-occurrence of SB and AB, and whether they have common correlates and also twin similarity of SB and AB bruxism traits by zygosity and sex. Methods A questionnaire was mailed to all twins born 1945-1957 in Finland in 2012 (n = 11 766). Age and sex adjusted logistic regression models were used. Twin similarity was assessed using polychoric correlations, and crosstwin-crosstrait correlations were computed. Results The response rate was 72% (n = 8410). Any SB was reported by 14.8% and >= 3 nights weekly by 5.0%. Percentages for any AB were 18.4% and 6.3%, respectively. There was substantial co-occurrence (29.5%) between SB and AB, and several shared correlates were found. For SB, the polychoric intra-class correlation was 0.366 in monozygotic (MZ) and 0.200 in dizygotic (DZ) pairs, without gender difference. A twofold crosstwin-crosstrait correlation was observed in MZ twins compared to DZ twins. Conclusions The risk factor profiles of SB and AB were largely but not entirely similar. The higher correlation in MZ than in DZ pairs suggests the influence of genetic factors on both SB and AB. The higher crosstwin-crosstrait correlation in MZ than in DZ pairs suggests some degree of genetic influences shared by SB and AB.
  • Masip, Guiomar; Keski-Rahkonen, Anna; Pietiläinen, Kirsi H.; Kujala, Urho M.; Rottensteiner, Mirva; Väisänen, Karoliina; Kaprio, Jaakko; Bogl, Leonie H. (2019)
    We constructed a food-based diet quality score (DQS) and examined its association with obesity measures, eating styles and nutrient intakes. Participants were 3592 individuals (764 dizygotic [DZ] and 430 monozygotic [MZ] twin pairs) from the FinnTwin16 study. The DQS (0-12 points) was constructed from a short 14 item food frequency questionnaire. Anthropometric measures and eating styles were self-reported. Nutrient intakes were calculated from food diaries completed in a subsample of 249 individuals (45 same-sex DZ and 60 MZ twin pairs). Twins were analyzed both as individuals and as twin pairs. The DQS was inversely associated with body mass index (beta = -0.12, per one-unit increase in DQS, p <0.001), waist circumference (beta = -0.34, p <0.001), obesity (odds ratio [OR]: 0.95, p = 0.004) and abdominal obesity (OR: 0.88, p <0.001), independent of sex, age, physical activity and education. A higher DQS was associated with health-conscious eating, having breakfast, less snacking, fewer evening meals, and a higher frequency and regularity of eating. The DQS was positively correlated with the intakes of protein, fiber and magnesium and negatively correlated with the intakes of total fat, saturated fat and sucrose. Within twin pairs, most of the associations between the DQS with eating styles and some nutrients remained, but the DQS was not associated with obesity measures within twin pairs. The DQS is an easy-to-use tool for ranking adults according to diet quality and shows an association with obesity measures, eating styles and key nutrients in the expected direction.
  • Dubois, Lise; Diasparra, Maikol; Bogl, Leonie-Helen; Fontaine-Bisson, Benedicte; Bedard, Brigitte; Tremblay, Richard E.; Kaprio, Jaakko; Boivin, Michel (2016)
    There is a lack of evidence pointing to specific dietary elements related to weight gain and obesity prevention in childhood and adulthood. Dietary intake and obesity are both inherited and culturally transmitted, but most prospective studies on the association between diet and weight status do not take genetics into consideration. The objective of this study was to document the association between dietary intake at 9 years and subsequent Body Mass Index (BMI) in adolescent monozygotic boy and girl twin pairs. This research used data from 152 twin pairs. Dietary data were collected from two 24-hour-recall interviews with a parent and the child aged 9 years. Height and weight were obtained when the twins were aged 9, 12, 13, and 14 years. Intrapair variability analysis was performed to identify dietary elements related to BMI changes in subsequent years. BMI-discordant monozygotic twin pairs were also identified to analyze the dietary constituents that may have generated the discordance. After eliminating potential confounding genetic factors, pre-adolescent boys who ate fewer grain products and fruit and consumed more high-fat meat and milk had higher BMIs during adolescence; pre-adolescent girls who consumed more grain products and high-fat meat and milk had higher BMIs during adolescence. Energy intake (EI) at 9 years was not related to BMI in subsequent years. Our study suggests that messages and interventions directed at obesity prevention could take advantage of sex-specific designs and, eventually, genetic information.
  • Silventoinen, Karri; Jelenkovic, Aline; Sund, Reijo; Yokoyama, Yoshie; Hur, Yoon-Mi; Cozen, Wendy; Hwang, Amie E.; Mack, Thomas M.; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Tomizawa, Rie; Pietilainen, Kirsi H.; Rissanen, Aila; Siribaddana, Sisira H.; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Tan, Qihua; Zhang, Dongfeng; Pang, Zengchang; Piirtola, Maarit; Aaltonen, Sari; Oncel, Sevgi Y.; Aliev, Fazil; Rebato, Esther; Hjelmborg, Jacob B.; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O.; Silberg, Judy L.; Eaves, Lindon J.; Cutler, Tessa L.; Ordonana, Juan R.; Sanchez-Romera, Juan F.; Colodro-Conde, Lucia; Song, Yun-Mi; Yang, Sarah; Lee, Kayoung; Franz, Carol E.; Kremen, William S.; Lyons, Michael J.; Busjahn, Andreas; Nelson, Tracy L.; Whitfield, Keith E.; Kandler, Christian; Jang, Kerry L.; Gatz, Margaret; Butler, David A.; Stazi, Maria A.; Fagnani, Corrado; D'Ippolito, Cristina; Duncan, Glen E.; Buchwald, Dedra; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Jeong, Hoe-Uk; Swan, Gary E.; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L.; Aslan, Anna K. Dahl; McAdams, Tom A.; Eley, Thalia C.; Gregory, Alice M.; Tynelius, Per; Baker, Laura A.; Tuvblad, Catherine; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Spector, Timothy D.; Mangino, Massimo; Lachance, Genevieve; Burt, S. Alexandra; Klump, Kelly L.; Harris, Jennifer R.; Brandt, Ingunn; Nilsen, Thomas S.; Krueger, Robert F.; Mcgue, Matt; Pahlen, Shandell; Corley, Robin P.; Huibregtse, Brooke M.; Bartels, Meike; van Beijsterveldt, Catharina E. M.; Willemsen, Gonneke; Goldberg, Jack H.; Rasmussen, Finn; Tarnoki, Adam D.; Tarnoki, David L.; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Hopper, John L.; Sung, Joohon; Maes, Hermine H.; Turkheimer, Eric; Boomsma, Dorret I.; Sorensen, Thorkild I. A.; Kaprio, Jaakko (2017)
    Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m(2))], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins >= 20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 2029 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
  • Kärkkäinen, Sanna; Pitkäniemi, Janne Mikael; Silventoinen, Karri; Svedberg, Pia; Huunan-Seppälä, Antti; Koskenvuo, Karoliina; Koskenvuo, Markku; Alexanderson, Kristina; Kaprio, Jaakko; Ropponen, Mari Annina (2013)
    OBJECTIVES: The aim of this study was to investigate the impact of work-related risk factors for future disability pension (DP) due to musculoskeletal diagnoses and for a subgroup of these, namely, DP due to osteoarthritis. METHODS: For this prospective study of 16 028 Finnish twins born in 1911-1957 and employed at baseline, a postal questionnaire collected information in 1975 on work-related factors; follow-up data on DP was gathered through register linkages up to 2004. A series of proportional hazards (Cox) regression models were used to analyze the associations between work-related factors and the incidence of DP. RESULTS: During the 30-year follow-up, 1297 participants (8%) were granted DP due to musculoskeletal diagnoses, 376 of which were due to osteoarthritis. High stress of daily activities, monotonous work, physical workload (namely work including lifting and carrying or physically heavy work), several workplace changes, and unemployment displayed a strong association with DP due to musculoskeletal diagnoses that was not affected by familial factors, including genetics and shared environment. Additionally, standing work increased the risk for DP due to osteoarthritis. CONCLUSIONS: Uninfluenced by family background or other confounding factors, several work-related factors were identified as being strong and direct risk factors for DP due to musculoskeletal diagnoses.
  • Sipila, Pyry; Rose, Richard J.; Kaprio, Jaakko (2016)
    AimsTo determine if associations of alcohol consumption with all-cause mortality replicate in discordant monozygotic twin comparisons that control for familial and genetic confounds. DesignA 30-year prospective follow-up. SettingPopulation-based older Finnish twin cohort. ParticipantsSame-sex twins, aged 24-60years at the end of 1981, without overt comorbidities, completed questionnaires in 1975 and 1981 with response rates of 89 and 84%. A total of 15607 twins were available for mortality follow-up from the date of returned 1981 questionnaires to 31December 2011; 14787 twins with complete information were analysed. MeasurementsSelf-reported monthly alcohol consumption, heavy drinking occasions (HDO) and alcohol-induced blackouts. Adjustments for age, gender, marital and smoking status, physical activity, obesity, education and social class. FindingsAmong twins as individuals, high levels of monthly alcohol consumption (259g/month) associated with earlier mortality [hazard ratio (HR)=1.63, 95% confidence interval (CI)=1.47-1.81]. That association was replicated in comparisons of all informatively drinking-discordant twin pairs (HR=1.91, 95% CI=1.49-2.45) and within discordant monozygotic (MZ) twin pairs (HR=2.24, 95% CI=1.31-3.85), with comparable effect size. Smaller samples of MZ twins discordant for HDO and blackouts limited power; a significant association with mortality was found for multiple blackouts (HR=2.82, 95% CI=1.30-6.08), but not for HDO. ConclusionsThe associations of high levels of monthly alcohol consumption and alcohol-induced blackouts with increased all-cause mortality among Finnish twins cannot be explained by familial or genetic confounds; the explanation appears to be causal.
  • Silventoinen, Karri; Jelenkovic, Aline; Latvala, Antti; Sund, Reijo; Yokoyama, Yoshie; Ullemar, Vilhelmina; Almqvist, Catarina; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Kandler, Christian; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Rebato, Esther; Stazi, Maria A.; Fagnani, Corrado; Brescianini, Sonia; Hur, Yoon-Mi; Jeong, Hoe-Uk; Cutler, Tessa L.; Hopper, John L.; Busjahn, Andreas; Saudino, Kimberly J.; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rose, Richard J.; Koskenvuo, Markku; Heikkilä, Kauko; Cozen, Wendy; Hwang, Amie E.; Mack, Thomas M.; Siribaddana, Sisira H.; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Nelson, Tracy L.; Whitfield, Keith E.; Tan, Qihua; Zhang, Dongfeng; Llewellyn, Clare H.; Fisher, Abigail; Burt, S. Alexandra; Klump, Kelly L.; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Medland, Sarah E.; Martin, Nicholas G.; Montgomery, Grant W.; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Aslan, Anna K. Dahl; Corley, Robin P.; Huibregtse, Brooke M.; OEncel, Sevgi Y.; Aliev, Fazil; Krueger, Robert F.; Mcgue, Matt; Pahlen, Shandell; Willemsen, Gonneke; Bartels, Meike; Van Beijsterveldt, Catharina E. M.; Silberg, Judy L.; Eaves, Lindon J.; Maes, Hermine H.; Harris, Jennifer R.; Brandt, Ingunn; Nilsen, Thomas S.; Rasmussen, Finn; Tynelius, Per; Baker, Laura A.; Tuvblad, Catherine; Ordonana, Juan R.; Sanchez-Romera, Juan F.; Colodro-Conde, Lucia; Gatz, Margaret; Butler, David A.; Lichtenstein, Paul; Goldberg, Jack H.; Harden, K. Paige; Tucker-Drob, Elliot M.; Duncan, Glen E.; Buchwald, Dedra; Tarnoki, Adam D.; Tarnoki, David L.; Franz, Carol E.; Kremen, William S.; Lyons, Michael J.; Maia, Jose A.; Freitas, Duarte L.; Turkheimer, Eric; Sorensen, Thorkild I. A.; Boomsma, Dorret I.; Kaprio, Jaakko (2017)
    Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
  • Yokoyama, Yoshie; Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Fagnani, Corrado; Stazi, Maria A.; Brescianini, Sonia; Ji, Fuling; Ning, Feng; Pang, Zengchang; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Rebato, Esther; Hopper, John L.; Cutler, Tessa L.; Saudino, Kimberly J.; Nelson, Tracy L.; Whitfield, Keith E.; Corley, Robin P.; Huibregtse, Brooke M.; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Llewellyn, Clare H.; Fisher, Abigail; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Krueger, Robert F.; McGue, Matt; Pahlen, Shandell; Bartels, Meike; van Beijsterveldt, Catharina E. M.; Willemsen, Gonneke; Harris, Jennifer R.; Brandt, Ingunn; Nilsen, Thomas S.; Craig, Jeffrey M.; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Haworth, Claire M. A.; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Rasmussen, Finn; Tynelius, Per; Tarnoki, Adam D.; Tarnoki, David L.; Ooki, Syuichi; Rose, Richard J.; Pietilainen, Kirsi H.; Sorensen, Thorkild I. A.; Boomsma, Dorret I.; Kaprio, Jaakko; Silventoinen, Karri (2018)
    Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.
  • Ji, Fuling; Ning, Feng; Duan, Haiping; Kaprio, Jaakko; Zhang, Dongfeng; Zhang, Dong; Wang, Shaojie; Qiao, Qing; Sun, Jianping; Liang, Jiwei; Pang, Zengchang; Silventoinen, Karri (2014)
  • Mohammadnejad, Afsaneh; Li, Weilong; Beltoft Lund, Jesper; Li, Shuxia; Larsen, Martin Jakob; Mengel-From, Jonas; Sheldrick-Michel, Tanja Maria; Christiansen, Lene; Christensen, Kaare; Hjelmborg, Jacob; Baumbach, Jan; Tan, Qihua (2021)
    Cognitive aging is one of the major problems worldwide, especially as people get older. This study aimed to perform global gene expression profiling of cognitive function to identify associated genes and pathways and a novel transcriptional regulatory network analysis to identify important regulons. We performed single transcript analysis on 400 monozygotic twins using an assumption-free generalized correlation coefficient (GCC), linear mixed-effect model (LME) and kinship model and identified six probes (one significant at the standard FDR < 0.05 while the other results were suggestive with 0.18 ≤ FDR ≤ 0.28). We combined the GCC and linear model results to cover diverse patterns of relationships, and meaningful and novel genes like APOBEC3G, H6PD, SLC45A1, GRIN3B, and PDE4D were detected. Our exploratory study showed the downregulation of all these genes with increasing cognitive function or vice versa except the SLC45A1 gene, which was upregulated with increasing cognitive function. Linear models found only H6PD and SLC45A1, the other genes were captured by GCC. Significant functional pathways (FDR < 3.95e-10) such as focal adhesion, ribosome, cysteine and methionine metabolism, Huntington's disease, eukaryotic translation elongation, nervous system development, influenza infection, metabolism of RNA, and cell cycle were identified. A total of five regulons (FDR< 1.3e-4) were enriched in a transcriptional regulatory analysis in which CTCF and REST were activated and SP3, SRF, and XBP1 were repressed regulons. The genome-wide transcription analysis using both assumption-free GCC and linear models identified important genes and biological pathways implicated in cognitive performance, cognitive aging, and neurological diseases. Also, the regulatory network analysis revealed significant activated and repressed regulons on cognitive function.
  • Li, Weilong; Baumbach, Jan; Mohammadnejad, Afsaneh; Lund, Jesper; Larsen, Martin Jakob; Hjelmborg, Jacob v. B.; Mengel-From, Jonas; Christensen, Kaare; Christiansen, Lene; Tan, Qihua (2020)
    Objective: The body mass index (BMI) measured as weight in relation to height is an important monitor for obesity and diabetes, with individual variation under control by genetic and environmental factors. In transcriptome-wide association studies on BMI, the genetic contribution calls for controlling of genetic confounding that affects both BMI and gene expression. We performed a global gene expression profiling of BMI on peripheral blood cells using monozygotic twins for efficient handling of genetic make-ups. Methods: We applied a generalized association method to genome-wide gene expression data on 229 pairs of monozygotic twins (age 56-80 years) for detecting diverse patterns of correlation between BMI and gene expression. Results: We detected seven probes associated with BMI with p<1e-04, among them two probes with p<1e-05 (p=2.83e-06 AAK1; p=7.83e-06 LILRA3). In total, the analysis found 1579 probes with nominal p<0.05. Biological pathway analysis of enriched pathways found 50 KEGG and 45 Reactome pathways (FDR<0.05). The identified top functional pathways included immune function, JAK-STAT signalling, insulin signalling and regulation of energy metabolism. Conclusion: This transcriptome-wide association study using monozygotic twins and generalized correlation identified differentially expressed genes and a broad spectrum of enriched biological pathways that may implicate metabolic health.
  • Heikkilä, Nelli; Vanhanen, Reetta; Yohannes, Dawit A.; Saavalainen, Päivi; Meri, Seppo; Jokiranta, T. Sakari; Jarva, Hanna; Mattila, Ilkka P.; Hamm, David; Sormunen, Silja; Saramäki, Jari; Arstila, T. Petteri (2020)
    We have analyzed T cell receptor repertoires in a unique set of thymus samples from a pair of monozygotic twins. While genetics affect the V(D)J rearrangement and generation of junctional sequences, the thymic selections seem largely stochastic and import no detectable inheritable effect at clonal level.
  • Hjelmborg, Jacob; Larsen, Pia; Kaprio, Jaakko; McGue, Matt; Scheike, Thomas; Hougaard, Philip; Christensen, Kaare (2019)
    Studies with twins provide fundamental insights to lifespans of humans. We aim to clarify if monozygotic and dizygotic twin individuals differ in lifespan, that is, if zygosity matters. We investigate whether a possible difference in mortality after infancy between zygosities is stable in different age cohorts, and whether the difference remains when twins with unknown zygosity are taken into account. Further, we compare the distribution of long-livers, that is, the upper-tail of the lifespan distribution, between monozygotic and same-sex dizygotic twin individuals. The Danish Twin Registry provides a nationwide cohort of 109,303 twins born during 1870 to 1990 with valid vital status. Standard survival analysis is used to compare mortality in monozygotic and dizygotic twin individuals and twin individuals with unknown zygosity. The mortality of monozygotic and dizygotic twin individuals differs slightly after taking into consideration effects of birth- and age-cohorts, gender differences, and that twins are paired. However, no substantial nor systematic differences remain when taking twins with unknown zygosity into account. Further, the distribution of long-livers is very similar by zygosity, suggesting the same mortality process. The population-based and oldest twin cohort ever studied suggests that monozygotic and dizygotic twins have similar lifespans.