| 1. |
- Abdellaoui, A, et al.
(författare)
-
CNV Concordance in 1,097 MZ Twin Pairs
- 2015
-
Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 18:1, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Monozygotic (MZ) twins are genetically identical at conception, making them informative subjects for studies on somatic mutations. Copy number variants (CNVs) are responsible for a substantial part of genetic variation, have relatively high mutation rates, and are likely to be involved in phenotypic variation. We conducted a genome-wide survey for post-twinning de novo CNVs in 1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two calling algorithms. In addition, CNV concordance rates were compared between the different sources of DNA, and gene-enrichment association analyses were conducted for thought problems (TP) and attention problems (AP) using CNVs concordant within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100 kb, of which the majority resided in 15q11.2. Based on the discordance of raw intensity signals a selection was made of 20 de novo CNVs for a qPCR validation experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in the same twin pair. The 13-year-old MZ twin pair that showed two discordances in CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From the remaining 18 putative de novo CNVs, 17 were deletions or duplications that were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV calls with CN ≠ 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but significantly higher concordance rate, and blood-derived DNA showed significantly more concordant CNVs per twin pair. The gene-enrichment analyses on concordant CNVs showed no significant associations between CNVs overlapping with genes involved in neuronal processes and TP or AP after accounting for the source of DNA.
|
|
| 2. |
- Adkins, DE, et al.
(författare)
-
Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood
- 2015
-
Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 18:4, s. 335-347
-
Tidskriftsartikel (refereegranskat)abstract
- The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
|
|
| 3. |
- Almqvist, Catarina, et al.
(författare)
-
Cohort profile : Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA)
- 2015
-
Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
-
Tidskriftsartikel (refereegranskat)abstract
- Asthma is a common childhood disease and several risk factors have been identified, however the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (parental interview at 9 or 12 years, N~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were identified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota) and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood and saliva sampling. This article describes the design, recruitment, data collection, measures, background characteristics as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development and new leads for prevention of asthma and allergic disease.
|
|
| 4. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
-
The Child and Adolescent Twin Study in Sweden (CATSS).
- 2011
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 14:6, s. 495-508
-
Tidskriftsartikel (refereegranskat)abstract
- The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing longitudinal twin study targeting all twins born in Sweden since July 1, 1992. Since 2004, parents of twins are interviewed regarding the children's somatic and mental health and social environment in connection with their 9th or 12th birthdays (CATSS-9/12). By January 2010, 8,610 parental interviews concerning 17,220 twins had been completed, with an overall response rate of 80%. At age 15 (CATSS-15) and 18 (CATSS-18), twins and parents complete questionnaires that, in addition to assessments of somatic and mental health, include measures of personality development and psychosocial adaptation. Twin pairs in CATSS-9/12 with one or both twins screening positive for autism spectrum disorders, attention deficit/hyperactivity disorder, tic disorders, developmental coordination disorder, learning disorders, oppositional defiant disorder, conduct disorder, obsessive-compulsive disorder, and/or eating problems have been followed with in-depth questionnaires on family, social environment and personality, and subsequently by clinical assessments at age 15 together with randomly selected population controls, including 195 clinically assessed twin pairs from the first 2 year cohorts (CATSS-15/DOGSS). This article describes the cohorts and study groups, data collection, and measures used. Prevalences, distributions, heritability estimates, ages at onset, and sex differences of mental health problems in the CATSS-9/12, that were analyzed and found to be overall comparable to those of other clinical and epidemiological studies. The CATSS study has the potential of answering important questions on the etiology of childhood mental health problems and their role in the development of later adjustment problems.
|
|
| 5. |
- Bahl, Aileen, et al.
(författare)
-
Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass
- 2015
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 18:6, s. 647-661
-
Tidskriftsartikel (refereegranskat)abstract
- The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.
|
|
| 6. |
- Bairnsfather, JE, et al.
(författare)
-
Investigating the Relationship Between Childhood Music Practice and Pitch-Naming Ability in Professional Musicians and a Population-Based Twin Sample
- 2022
-
Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 25:3, s. 140-148
-
Tidskriftsartikel (refereegranskat)abstract
- The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins (N = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic (r = .27, p < .001) but not dizygotic twin pairs (r = −.04, p = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy (p = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose–response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice.
|
|
| 7. |
- Baker, Laura, et al.
(författare)
-
The Southern California twin register at the University of Southern California : III
- 2013
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 16:1, s. 336-343
-
Tidskriftsartikel (refereegranskat)abstract
- The Southern California Twin Register at the University of Southern California (USC) was initiated in 1984 and continues to provide an important resource for studies investigating genetic and environmental influences on human behavior. This article provides an update on the current register and its potential for future twin studies using recruitment through school district databases and voter records. An overview is also provided for an ongoing longitudinal twin study investigating the development of externalizing psychopathology from childhood to young adulthood, the USC Study of Risk Factors for Antisocial Behavior. Characteristics of the twins and their families are presented, including recruitment and participation rates, as well as attrition analyses and a summary of key findings to date.
|
|
| 8. |
- Bladh, Marie, et al.
(författare)
-
Hospitalization in Adolescence and Young Adulthood Among Twins and Singletons : A Swedish Cohort Study of Subjects Born Between 1973 and 1983
- 2013
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 16:3, s. 707-715
-
Tidskriftsartikel (refereegranskat)abstract
- Children born with non-optimal birth characteristics — that is, are small for gestational age and/or preterm — have an increased risk for several long-term effects such as neurological sequelae and chronic disease. The purpose of this study was to examine whether twins exhibited a different outcome, compared with singletons, in terms of hospitalization during adolescence and early adulthood, and to what extent differences remain when considering the divergence in birth characteristics between singletons and twins. Persons born between 1973 and 1983 in Sweden and surviving until age 13 were included and followed until the end of 2006. Data on birth characteristics, parental socio-demographic factors, and hospitalizations were collected from national registers. Adjusting for parental socio-demographic factors, twins had a higher risk of being hospitalized than singletons (odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10–1.25) and more often due to ‘Congenital anomalies’ (OR = 1.18, 95% CI = 1.06–1.28), ‘Infections’ (OR = 1.14; 95% CI = 1.08–1.20), ‘External causes of illness’ (OR = 1.10, 95% CI = 1.06–1.15), and ‘Diseases of the nervous system’ (OR = 1.18, 95% CI = 1.10–1.26). Stratifying for birth characteristics, this difference diminishes, and for some diagnoses non-optimal twins seem to do slightly better than non-optimal singletons. Thus, twins with non-optimal birth characteristics had a lower risk of hospitalization than non-optimal singletons on, for example, ‘Congenital anomalies’ and ‘Diseases of the nervous system’ (OR = 0.86, 95% CI = 0.77–0.96; OR = 0.88, 95% CI = 0.81–0.97, respectively) and Total (any) hospitalization (OR = 0.87, 95% CI = 0.83–0.92). Among those with optimal birth characteristics, twins had an increased hospitalization due to ‘External causes of illness’ (OR = 1.07, 95% CI = 1.02–1.13) compared with optimal singletons. Twins have higher hospitalization rates than singletons. In stratifying for birth characteristics, this difference diminishes, and for some diagnoses, non-optimal twins seem to do less poorly than non-optimal singletons.
|
|
| 9. |
- Bladh, Marie, et al.
(författare)
-
Intergenerational cohort study of preterm and small-for-gestational-age birth in twins and singletons
- 2015
-
Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 581-590
-
Tidskriftsartikel (refereegranskat)abstract
- To date several studies have investigated the intergenerational effect of preterm and small-for-gestational-age births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and small for gestational age (SGA) among twins and singletons.A prospective population based register study of mother-first-born offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4073 twins and 264,794 singletons born in 1973-1983 and their firstborns born in 1986-2009. Preterm birth was defined as birth <37 weeks of gestation and SGA as < 2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers and mother’s socio-demographic factors in addition to maternal birth- characteristics.Among mothers born as singletons, being born preterm was associated with an increased risk for delivering a preterm child (adjusted OR 1.39, 95% CI 1.29-1.50) while being born SGA increased the likelihood of a SGA child (adjusted OR 3.04, 95% CI 2.80-3.30) as well as a preterm child (adjusted OR 1.30, 95% CI 1.20-1.40). In twin mothers, the corresponding ORs tended to be lower and the only statistically significant association was between a SGA mother and a SGA child (adjusted OR 2.15, 95% CI 1.40-3.31). A statistically significant interaction between twinning and mother’s size for gestational was identified in a multivariate linear regression analysis indicating that singleton mothers born SGA were associated with a lower birth weight compared to mothers not born SGA.Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons.
|
|
| 10. |
- Bolte, S., et al.
(författare)
-
The Roots of Autism and ADHD Twin Study in Sweden (RATSS)
- 2014
-
Ingår i: Twin Research and Human Genetics. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:3, s. 164-176
-
Tidskriftsartikel (refereegranskat)abstract
- Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.
|
|
