Prospective Twin Cohort Study Research Articles

Heritability of tear fluid cytokines in healthy twins

PurposeOcular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid inflammatory markers are lacking. New knowledge may help guide research into ocular surface disease biomarkers and therapeutics. MethodsIn this prospective twin cohort study, healthy individuals were recruited from a population-based registry. Tear fluid was collected with the Schirmer test strips was submerged in phosphate buffered saline and stored at −80° before undergoing 27-cytokine multiplex immunoassay analysis. Broad-sense heritability (h2) of cytokine concentrations was analyzed. Results90 participants (23 monozygotic and 22 dizygotic twin pairs) were included. Data availability allowed for heritability analysis of 15 cytokines, and a h2 >50% was seen for 10 cytokines. A statistical power of >80% was achieved for heritability analyses of the cytokines interferon gamma induced protein 10 (h2 = 94.8%), eotaxin (89.8%), interleukin 7 (86.6%), interleukin 1β (82.2%) and monocyte chemoattractant protein 1 (68.2%). ConclusionsThe tear fluid concentration of several analyzed cytokines was found to be highly heritable. A considerable amount of the inter-individual variation observed for the concentration of certain tear fluid cytokines can be linked to hereditary factors that cannot easily be modified by changing factors in the environment of patients. This suggests that a higher success in ocular surface disease drug discovery may be anticipated for drugs that have targets in specific populations, and points to the importance of emphasizing known preventive measures of ocular surface disease and examinations of close relatives of patients with ocular surface disease, such as dry eye disease.

Three trajectories of gestational weight gain identified in an Australian twin study

ObjectivesGestational weight gain (GWG) has been associated with maternal and child health outcomes, but knowledge of appropriate GWG for twin gestations is limited. Study designThe Peri/Postnatal Epigenetic Twins Study is a prospective twin cohort study of 250 women and their twin children in Melbourne, Australia. We modeled trajectories of GWG using group-based growth modeling and compared these trajectories to GWG categories (within, above, or below current GWG recommendations for twin pregnancy). We fitted robust linear and Poisson regression models to assess associations of maternal pre-pregnancy and gestational exposures with risk of gaining weight outside the recommendations. ResultsOf the 250 women enrolled in the PETS, GWG measures were available for 172 women. Forty-seven percent of women had GWG within the current recommendations. We identified three GWG trajectories – 23.6% of women had low GWG throughout pregnancy, 34.5% had average GWG throughout pregnancy, and 42.0% had average initial GWG, followed by high GWG from trimester two until delivery. Gestational diabetes mellitus (GDM) was associated with increased risk of inadequate GWG (RR: 2.40, 95%CI: 1.53, 3.75). Pre-pregnancy obesity (RR: 1.88, 95%CI: 1.09, 3.26) and hypertensive disorders of pregnancy (RR: 2.64, 95%CI: 1.20, 5.81) were associated with increased risk of excessive GWG. ConclusionsMore than half of the women in the PETS did not meet the current GWG recommendations. Women with GDM or hypertensive disorders were more likely to gain weight outside these guidelines. More research is needed to establish comprehensive guidelines for twin pregnancies.

Psychosocial Working Conditions and Subsequent Sickness Absence-Effects of Pain and Common Mental Disorders in a Population-Based Swedish Twin Sample.

To investigate pain and/or common mental disorders (CMDs) in the associations between psychosocial working conditions and sickness absence (SA) while controlling familial confounding. Prospective Prospective twin cohort study included survey data for pain and CMD, register data for SA and psychosocial working conditions. The follow-up from 2005 to 2016 of 28,916 twin individuals for first incident SA spell measured as the main International Classification of Diseases version 10 (ICD-10) diagnosis groups (F00-F99, I00-I99, and M00-M99), or the duration. We used regression models to obtain odds ratio (OR), incidence rate ratio (IRR), or relative risk ratio (RRR) with 95% confidence intervals (CI). The covariate adjusted models of 9156 SA spells indicated almost no statistically significant associations between psychosocial working conditions and SA. Psychosocial working conditions were not associated with SA while familial confounding could not be ruled out.

Association of Age at Myopia Onset With Risk of High Myopia in Adulthood in a 12-Year Follow-up of a Chinese Cohort

Early-onset myopia is well known to progress to high myopia in adulthood. However, no accurate estimation of how a specific age at myopia onset is associated with the probability of developing high myopia in adulthood is available, and a very-long-term follow-up study with data from annual visits is needed. To estimate the risk of developing high myopia in adulthood associated with a specific age at myopia onset from a data set with a 12-year annual follow-up. This ongoing, population-based prospective cohort study of twins was conducted in Guangzhou, China, on July 11, 2006. Data from baseline to August 31, 2018, were analyzed. The first-born twins completed follow-up until 17 years or older, and the 443 participants (after exclusions) who developed myopia were included in the analysis. Data were analyzed from September 1, 2018, to January 20, 2020. Age at myopia onset was determined by prospective annual cycloplegic refractions (365 participants [82.4%]) or with a questionnaire. Refraction in adulthood was defined as the cycloplegic refraction measured at the last follow-up visit. Among the 443 eligible participants (247 [55.8%] female; mean [SD] age at myopia onset, 11.7 [2.0] years), 54 (12.2%) developed high myopia (spherical equivalent, -6.00 diopters or worse determined by cycloplegic refractions) in adulthood. Among participants with age at myopia onset of 7 or 8 years, 14 of 26 (53.9%; 95% CI, 33.4%-73.4%) developed high myopia in adulthood; among those with onset at 9 years of age, 12 of 37 (32.4%; 95% CI, 18.0%-49.8%); among those with onset at 10 years of age, 14 of 72 (19.4%; 95% CI, 11.1%-30.5%); among those with onset at 11 years of age, 11 of 78 (14.1%; 95% CI, 7.3%-23.8%); and among those with onset at 12 years or older, 3 of 230 (1.3%; 95% CI, 0.2%-3.8%). Results of multivariate logistic regression analysis suggested that the risk of developing high myopia in adulthood decreased significantly with delay in the age at myopia onset (odds ratio, 0.44; 95% CI, 0.36-0.55; P < .001), from greater than 50% for 7 or 8 years of age to approximately 30% for 9 years of age and 20% for 10 years of age. These findings suggest that the risk of high myopia is relatively high in children with myopia onset during the early school ages. Each year of delay in the age at onset substantially reduces the chance of developing high myopia in adulthood, highlighting the importance of identifying effective prevention strategies under investigation, such as increasing outdoor time.

Anorexia nervosa and autism: a prospective twin cohort study.

Anorexia nervosa (AN) and autism spectrum disorder (ASD) may be phenotypically and etiologically linked. However, due to the absence of prospective studies, it remains unclear whether the elevation of autistic traits in AN is evident in early childhood. Here, we prospectively investigated autistic traits before and after the first diagnosis of AN. In a population-based sample of 5,987 individuals (52.4% female) from the Child and Adolescent Twin Study in Sweden, parents reported autistic traits at ages 9 and 18. AN and ASD diagnoses were retrieved from the Swedish National Patient Register. In addition, AN diagnoses were ascertained by parent-reported treatment for AN. We compared whether individuals with and without AN differed in autistic traits before the first diagnosis of AN (age 9) and after the first diagnosis of AN (age 18). We did not find evidence for elevated autistic traits in 9-year-old children later diagnosed with AN. At age 18, however, there was a marked elevation in restricted/repetitive behavior and interests, but only in the subgroup of individuals with acute AN. A less pronounced elevation was observed for social communication problems. Coping strategies in individuals with ASD and the somewhat different female ASD phenotype may explain why we did not find elevated autistic traits in children who later developed AN. Alternatively, it is possible that elevated autistic traits were not present prior to the onset of AN, thus questioning the previously reported elevated prevalence of ASD in AN. Future studies should use tailored measurements in order to investigate whether autistic traits in individuals with AN are best conceptualized as an epiphenomenon of the acute AN phase or whether these symptoms indeed represent ASD as a clinically verifiable neurodevelopmental disorder.

Anorexia nervosa and autism: a prospective twin cohort study

Anorexia nervosa and autism: a prospective twin cohort study

The role of occupational class on the association between sickness absence and disability pension: A Swedish register-based twin study.

Objectives The aim of this study was to examine the association between long-term sickness absence (LTSA) due to mental disorders and musculoskeletal disorders and all-cause disability pension (DP) among blue- and white-collar workers. A secondary objective was to examine the influence of familial factors on the associations. Methods This was a prospective twin cohort study of 42 984 individuals (21-64 years at baseline), 3017 of whom had a new LTSA spell (>14 days) due to mental or musculoskeletal disorders in 2005-2006. Average follow-up time was 5.4 years. Survey data on occupational class and register data on LTSA and DP were used. Cox proportional hazards regression was applied to calculate hazards ratios (HR) with 95% confidence intervals (CI). Results During follow-up, 989 participants went on disability. LTSA due to mental disorders and musculoskeletal disorders led to similar HR for DP among both white- and blue-collar workers when compared to white-collar workers not on LTSA (reference group). LTSA ≥6 months due to musculoskeletal disorders was associated with a higher risk of DP for white-collar (HR 31.50, 95% CI 20.45-48.52) than blue-collar (HR 17.64, 95% CI 13.08-23.78) workers when compared to the reference group. HR were lower in the discordant twin pair models for LTSA due to mental disorders than in the whole cohort. Conclusions White-collar workers on LTSA due to musculoskeletal disorders are especially vulnerable to all-cause DP. This pattern was not present for LTSA due to mental disorders. Familial factors seem to influence the association between LTSA due to mental disorders and all-cause DP.

Long-term leisure-time physical activity and other health habits as predictors of objectively monitored late-life physical activity \u2013 A 40-year twin study

Moderate-to-vigorous physical activity (MVPA) in old age is an important indicator of good health and functional capacity enabling independent living. In our prospective twin cohort study with 616 individuals we investigated whether long-term physical activity assessed three times, in 1975, 1982 and 1990 (mean age 48 years in 1990), and other self-reported health habits predict objectively measured MVPA measured with a hip-worn triaxial accelerometer (at least 10 hours per day for at least 4 days) 25 years later (mean age of 73 years). Low leisure-time physical activity at younger age, higher relative weight, smoking, low socioeconomic status, and health problems predicted low MVPA in old age in individual-based analyses (altogether explaining 20.3% of the variation in MVPA). However, quantitative trait modeling indicated that shared genetic factors explained 82% of the correlation between baseline and follow-up physical activity. Pairwise analyses within monozygotic twin pairs showed that only baseline smoking was a statistically significant predictor of later-life MVPA. The results imply that younger-age physical activity is associated with later-life MVPA, but shared genetic factors underlies this association. Of the other predictors mid-life smoking predicted less physical activity at older age independent of genetic factors.

Breastfeeding and IQ Growth from Toddlerhood through Adolescence.

ObjectivesThe benefits of breastfeeding for cognitive development continue to be hotly debated but are yet to be supported by conclusive empirical evidence.MethodsWe used here a latent growth curve modeling approach to test the association of breastfeeding with IQ growth trajectories, which allows differentiating the variance in the IQ starting point in early life from variance in IQ gains that occur later in childhood through adolescence. Breastfeeding (yes/ no) was modeled as a direct predictor of three IQ latent growth factors (i.e. intercept, slope and quadratic term) and adjusted for the covariates socioeconomic status, mother's age at birth and gestational stage. Data came from the Twins Early Development Study (TEDS), a prospective cohort study of twins born between 1996 and 1994 in the United Kingdom, who were assessed 9 times on IQ between age 2 and 16 years (N = 11,582).ResultsHaving been breastfed was associated with a small yet significant advantage in IQ at age 2 in girls (β = .07, CI 95% from 0.64 to 3.01; N = 3,035) but not in boys (β = .04, CI 95% from -0.14 to 2.41). Having been breastfeeding was neither associated with the other IQ growth factors in girls (slope: β = .02, CI 95% from -0.25 to 0.43; quadratic: β = .01, CI 95% from -0.02 to 0.02) nor in boys (slope: β = .02, CI 95% from -0.30 to 0.47; quadratic: β = -.01, CI 95% from -0.01 to 0.01).ConclusionsBreastfeeding has little benefit for early life intelligence and cognitive growth from toddlerhood through adolescence.

A prospective twin cohort study of disability pensions due to musculoskeletal diagnoses in relation to stability and change in pain

Pain is known to play an important role in the pathway to becoming work disabled, in particular for award of disability pensions (DP) due to musculoskeletal diagnoses (MSD). This prospective cohort study investigated MSD-related pain stability and/or changes as predictors for DP during a 23-year follow-up. Additionally confounding factors were examined to elucidate whether familial effects (including genetics and family background) or socioeconomic status, other pain, or use of medication would affect the associations between pain and DP. Data were available on 11,224 twins (4399 complete pairs) born before 1958 surveyed through questionnaires about background factors and musculoskeletal (low back, neck, and shoulder) pain impairing work ability in 1975 and 1981. The follow-up data were collected from pension registers until 2004. Cox proportional hazards regression models were used. During the 23-year follow-up, 508 DPs due to MSD, 166 DPs due to osteoarthritis (OA), and 162 DPs due to low back diagnoses (LBD) were granted. Musculoskeletal pain impairing work ability both measured at 1 time point and 6 years apart, and either 1 pain location or multiple locations, predicted increased risk for DP due to MSD, OA, and LBD. The associations were independent of familial confounding factors and of several influential background factors, including headache; migraine; use of analgesics, hypnotics, or tranquillizers; life satisfaction; and education and marital status. This study concluded that musculoskeletal pain impairing work ability is an early and direct predictor for DP due to MSD, OA, and LBD.

Does smoking among friends explain apparent genetic effects on current smoking in adolescence and young adulthood?

We used data from a prospective cohort study of twins to investigate the influence of unmeasured genetic and measured and unmeasured environmental factors on the smoking behaviour of adolescents and young adults. Twins were surveyed in 1988 (aged 11–18 years), 1991, 1996 and 2004 with data from 1409, 1121, 732 and 758 pairs analysed from each survey wave, respectively. Questionnaires assessed the smoking behaviour of twins and the perceived smoking behaviour of friends and parents. Using a novel logistic regression analysis, we simultaneously modelled individual risk and excess concordance for current smoking as a function of zygosity, survey wave, parental smoking and peer smoking. Being concordant for having peers who smoked was a predictor of concordance for current smoking (P<0.001). After adjusting for peer smoking, monozygotic (MZ) pairs were no more alike than dizygotic pairs for current smoking at waves 2, 3 and 4. Genetic explanations are not needed to explain the greater concordance for current smoking among adult MZ pairs. However, if they are invoked, the role of genes may be due to indirect effects acting through the social environment. Smoking prevention efforts may benefit more by targeting social factors than attempting to identify genetic factors associated with smoking.

Physical activity in adolescence and smoking in young adulthood: a prospective twin cohort study

To control for familial confounds, we studied the association between adolescent physical activity and later smoking in twin siblings discordant for their baseline physical activity. In this prospective population-based twin study, we asked whether persistent physical activity/inactivity in adolescence (assessed at 16, 17 and 18.5 years) predicted questionnaire-reported daily smoking at ages 22-27. Twins who, on the three baseline questionnaires, consistently reported frequent leisure physical activity (more than three times weekly) were classified as persistent exercisers, those who exercised less than three times monthly were called persistently inactive, others were occasional exercisers. Finland. A total of 4240 individuals, including 1870 twin pairs. Findings In analyses of individual twins, compared to persistent activity, persistent physical inactivity predicted increased risk of daily smoking (age- and sex-adjusted odds ratio 5.53, 95% confidence interval 3.88-7.88, P < 0.001). The risk remained elevated even after excluding all those who had smoked 50 cigarettes or more life-time at baseline and adjusted for educational level in adolescence. In within-pair analyses compared to the active members of discordant twin pairs, the physically inactive co-twins had increased risk of future daily smoking (sex-adjusted odds ratio 3.39, 95% confidence interval 1.56-7.39, P = 0.002). Persistent physical inactivity in adolescence relates to adult smoking, even after familial factors are taken into account.

Eating styles, overweight and obesity in young adult twins

To explore the association of eating styles with overweight and obesity in young adults, controlling for identical genetic background in monozygotic twins. Prospective twin cohort study. Finland, 1991-2002. Two-hundred and thirty-three women and 2060 men from the FinnTwin16 study, aged 16 years at baseline (T1), and ranging from 22 to 27 years at the time of the nutritional assessment (T4). Eating styles (Restrictive/overeating, health-conscious, snacking, emotional and externally induced), self-reported at T4, were contrasted with body mass indices (BMIs) at T1 and T4. At T4, obesity (BMI>or=30Kg/m(2)) was significantly cross-sectionally associated with restrictive eating, frequent snacks, eating in the evening, avoiding fatty foods and failure to maintain healthy eating patterns. These associations were independent of BMI at T1. Obese women self-reported more vulnerability to external eating cues and comfort eating than normal-weight women. However, in a multivariable model, only restrictive/overeating and health-conscious eating styles were significant correlates of obesity at T4, independent of gender and BMI at T1. When we controlled for genetic background restricting the analysis to the 39 female and 45 male monozygotic twin pairs discordant for obesity or overweight (BMI>or=25Kg/m(2)), restrictive/overeating eating style was still statistically significantly associated with excess weight. The eating styles of obese young adults differ from their normal-weight counterparts: restrictive eating, overeating and fewer healthy food choices are associated with obesity. Different eating styles may partially explain weight differences in individuals with identical genetic background.

Perinatal and Early Childhood Outcomes of Twins Versus Triplets

AbstractThe purpose of this prospective cohort study of twins and triplets was to evaluate perinatal and early childhood outcomes through 18 months of age. The study population included 141 twin pregnancies (282 twin children) and 8 triplet pregnancies (24 triplet children) recruited between May, 1996 and June, 2001. Mothers of triplets versus twins were significantly more likely to have infertility treatments, to be overweight or obese before conception, to be admitted antenatally, and to deliver by cesarean section. Length of gestation for triplets was significantly shorter (–2.31 weeks,p&lt; .0001), and more likely to be less than 35 weeks (Adjusted Odds Ratio [AOR] 9.38, 95% confidence interval [CI] 3.22–27.29). Average birthweight for triplets was significantly lighter (–495 grams,p&lt; .0001), and more likely to be low birthweight (AOR 11.38, 95% CI 3.11–41.61). Triplets were also more likely to be admitted to neonatal intensive care (AOR 7.97, 95% CI 2.13–29.77), to require mechanical ventilation (AOR 5.67, 95% CI 2.05–15.65), to develop respiratory distress syndrome (AOR 12.50, 95% CI 3.89–40.20), or a major morbidity (retinopathy of prematurity, necrotizing enterocolitis, ventilator support, or grade III or IV intraventricular hemorrhage, AOR 5.67, 95% CI 2.05–15.65). Weight, length, and head circumference was significantly smaller at birth for triplets compared to twins, and these differences remained through 18 months of age, along with lower mental developmental scores at the oldest age. Compared to twins, triplets have greater neonatal morbidity, and through 18 months of age lower mental and motor scores, slower postnatal growth and more residual stunting, particularly of length and head circumference.

Perinatal and Early Childhood Outcomes of Twins Versus Triplets

The purpose of this prospective cohort study of twins and triplets was to evaluate perinatal and early childhood outcomes through 18 months of age. The study population included 141 twin pregnancies (282 twin children) and 8 triplet pregnancies (24 triplet children) recruited between May, 1996 and June, 2001. Mothers of triplets versus twins were significantly more likely to have infertility treatments, to be overweight or obese before conception, to be admitted antenatally, and to deliver by cesarean section. Length of gestation for triplets was significantly shorter (-2.31 weeks, p < .0001), and more likely to be less than 35 weeks (Adjusted Odds Ratio [AOR] 9.38, 95% confidence interval [CI] 3.22-27.29). Average birthweight for triplets was significantly lighter (-495 grams, p < .0001), and more likely to be low birthweight (AOR 11.38, 95% CI 3.11-41.61). Triplets were also more likely to be admitted to neonatal intensive care (AOR 7.97, 95% CI 2.13-29.77), to require mechanical ventilation (AOR 5.67, 95% CI 2.05-15.65), to develop respiratory distress syndrome (AOR 12.50, 95% CI 3.89-40.20), or a major morbidity (retinopathy of prematurity, necrotizing enterocolitis, ventilator support, or grade III or IV intraventricular hemorrhage, AOR 5.67, 95% CI 2.05-15.65). Weight, length, and head circumference was significantly smaller at birth for triplets compared to twins, and these differences remained through 18 months of age, along with lower mental developmental scores at the oldest age. Compared to twins, triplets have greater neonatal morbidity, and through 18 months of age lower mental and motor scores, slower postnatal growth and more residual stunting, particularly of length and head circumference.