MZ Twins Research Articles

P121 Background of the Development of Carotid and Femoral Atherosclerotic Plaques in Twins

IntroductionDevelopment of carotid and femoral atherosclerotic plaques proved to be heritable in previous studies. However, no comprehensive ultrasonographic evaluation of the volume and types of plaque has been performed.MethodsComprehensive carotid and femoral arterial ultrasound examination (Samsung RS85, arterial analysis, 15 MHz probe) was performed in 92 Hungarian twins (54 monozygotic, MZ and 38 dizygotic, DZ twin pairs, mean age 54 ± 13 years). The volume of plaques was automatically measured, and the plaque type was grouped according to echogenicity. Raw heritability was evaluated using the Falconer formula.ResultsNo heritability of the total number of carotid and femoral plaques and total plaque volume was detected. Although the number of carotid plaques themselves has been found to be hereditary (h2 = 0.492), the volume of carotid and femoral plaques as well as the number of femoral plaques were not heritable. More MZ twin pairs were discordant in the presence of soft plaques in the carotid artery as DZ twin pairs, but greater similarity in femoral plaques was not detected between MZ twins, which does not indicate a genetic background. The presence of calcified and mixed echogenic carotid plaques in the MZ twins was more concordant as in DZ twins, indicating inheritance.ConclusionThe total number and volume of carotid and femoral plaques are influenced by the environment. Different plaque types have different backgrounds: while calcified and mixed echogenic carotid plaques are more affected by genetics, soft carotid and femoral plaques are more affected by the environment.

Negligible heritability of language laterality assessed by functional transcranial Doppler ultrasound: a twin study

Background: It is widely assumed that individual differences in language lateralisation have a strong genetic basis, yet prior studies show low heritability (around 0.25) for the related trait of handedness, and two twin studies of structural brain asymmetry obtained similarly low estimates. This report describes heritability estimates from a twin study of language laterality and handedness phenotypes. Methods: The total sample consisted of 194 twin pairs (49% monozygotic) aged from 6 to 11 years. A language laterality index was obtained for 141 twin pairs, who completed a protocol where relative blood flow through left and right middle cerebral arteries was measured using functional transcranial Doppler ultrasound (fTCD) while the child described animation sequences. Handedness data was available from the Edinburgh Handedness Inventory (EHI) and Quantification of Hand Preference (QHP) for all 194 pairs. Heritability was assessed using conventional structural equation modeling, assuming no effect of shared environment (AE model). Results: For the two handedness measures, heritability estimates were consistent with prior research: 0.23 and 0.22 respectively for the EHI and QHP. For the language laterality index, however, the twin-cotwin correlations were very close to zero for both MZ and DZ twins, and the heritability estimate was zero. Conclusions: A single study showing negligible heritability for language laterality cannot rule out a genetic effect on language lateralisation. It is possible that the low twin-cotwin correlations were affected by noisy data: although the split-half reliability of the fTCD-based laterality index was high (0.85), we did not have information on test-retest reliability in children, which is likely to be lower. We cannot rule out the possibility that true heritability of differences in language lateralization is non-zero, but results indicate that the heritability of this trait is low at best. Stochastic variation in neurodevelopment appears to play a major role in determining cerebral lateralisation.

Development of a Food-Based Diet Quality Score from a Short FFQ and Associations with Obesity Measures, Eating Styles and Nutrient Intakes in Finnish Twins.

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 (β = −0.12, per one-unit increase in DQS, p < 0.001), waist circumference (β = −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.

Multi-omics study in monozygotic twins confirm the contribution of de novo mutation to psoriasis

BackgroundGenome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.0 in Chinese population. Although rare variations still account for a small proportion of phenotypic variances in complex diseases, their effect on phenotypes is large. Recently, more and more studies focus on the low-frequency functional variants and have achieved a certain amount of success. MethodWhole genome sequencing and sanger sequencing was performed on 8 MZ twin pairs discordant for psoriasis to scan and verified the de novo mutations (DNMs). Additionally, 665 individuals with about 20 years' medical history versus 2054 healthy controls and two published large population studies which had about 8 years’ medical history (including 10,727 cases versus 10,582 controls) were applied to validate the enrichment of rare damaging mutations in two DNMs genes. Besides, to verify the pathogenicity of candidate DNM in C3, RNA-sequencing for CD4+, CD8+ T cells of twins and lesion, non-lesion skin of psoriasis patients were carried out. Meanwhile, the enzyme-linked immunosorbent assay kit was used to detect the level of C3, C3b in the supernatant of peripheral blood. ResultA total of 27 DNMs between co-twins were identified. We found six of eight twins carry HLA-C∗0602 allele which have large effects on psoriasis. And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele. In the replication stage, we found 2 loss-of-function (LOF) variants of C3 only in 665 cases with about 20 years' medical history and gene-wise analysis in 665 cases and 2054 controls showed that the rare missense mutations in C3 were enriched in cases (OR = 1.91, P = 0.0028). We further scanned the LOF mutations of C3 in two published studies (about 8 years’ medical history), and found one LOF mutation in the case without carrying HLA-C*0602. In the individual with DNM in C3, RNA sequencing showed the expression level of C3 in skin was significant higher than healthy samples in public database (TPM fold change = 1.40, P = 0.000181) and ELISA showed protein C3 in peripheral blood was higher (~2.2-fold difference) than the other samples of twins without DNM in C3. ConclusionTo the best of our knowledge, this is the first report that DNM in C3 is the likely pathological mutations, and it provided a better understanding of the genetic etiology of psoriasis and additional treatments for this disease.

Identification of Disease-associated Traits and Clonotypes in the T Cell Receptor Repertoire of Monozygotic Twins Affected by Inflammatory Bowel Diseases.

Background and AimsIntestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers.MethodsEmploying unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD.ResultsWe observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins.ConclusionsOur findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes.

Exploring of rare differences in mtGenomes between MZ twins using massively parallel sequencing

Compared with nuclear DNA, fewer DNA repair mechanisms in mitochondria and lack of proofreading capabilities in the mtDNA polymerase help introduce more variability between MZ twins. In our previous study, we used ultra-deep mtGenome sequencing to characterize point heteroplasmy and nucleotide variant in blood samples of MZ twins. In the present study, we characterize minor differences of mtGenomes in saliva and hair shaft samples from six sets of MZ twins using the Precision ID mtDNA Whole Genome Panel, Ion S5 XL system, and Converge Software. Additionally, the effectiveness of different tissue samples for differentiating between MZ twins was evaluated. Point heteroplasmies were observed in all sets of MZ twins regardless of sample type. Overall, more variants were observed in the mtGenome from hair shaft samples than that from blood and saliva samples. The results of this study further support that the mtGenome analysis could be used to distinguish MZ twins from each other.

Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.

We performed a comprehensive assessment of rareinherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk genes, most supported by rare inherited variants, a substantial extensionof previousfindings. Biological pathways enriched for genes harboring inherited variants represent cytoskeletal organization and ion transport, which are distinct from pathways implicated in previous studies. Nevertheless, the de novo and inherited genes contribute to a common protein-protein interaction network. We also identified structural variants (SVs) affecting non-coding regions, implicating recurrent deletions in the promoters of DLG2 and NR3C2. Loss of nr3c2 function in zebrafish disrupts sleep and social function, overlapping with human ASD-related phenotypes. These data support the utility of studying multiplex families in ASD and are available through the Hartwell Autism Research and Technology portal.

Deciphering the role of epigenetics in self-limited epilepsy with centrotemporal spikes

ObjectiveThe aetiology of self-limited epilepsy with centro-temporal spikes (SECTS) remains controversial and a strong genetic basis has long been presumed. The discordant monozygotic twin (MZ) model controls for shared genetic and environmental factors, enabling focus on the potential role of the non-shared environment. MethodsDNA methylation data was acquired from DNA extracted from three discordant MZ twin pairs, from both new born blood spots before epilepsy onset, and blood samples taken after epilepsy onset. An epigenome-wide analysis was performed, using the Illumina Infinium EPIC array. Differentially methylated regions (DMR) were identified using the bumphunter package in R. Comparative analyses were undertaken at the two different time points as well as a combined analysis independent of time. ResultsMany of the top DMR-associated genes have previously been described in neurodevelopmental disorders. The LYPD8 gene was associated with a top-ranked DMR both at birth and across the two time points. ConclusionWe have demonstrated the novel utility of the longitudinal, discordant MZ twin model, to facilitate a deeper appreciation of the complex neurobiology of SECTS. The genetic architecture of SECTS is complex and is likely to involve an interplay between genes and environment, in part mediated by epigenetics.

Perceived Stress and Sleep Quality in Midlife and Later: Controlling for Genetic and Environmental Influences

ABSTRACT Objective/Background Stress is a strong predictor for poor sleep quality. However, little is known about the mechanism of this association or the respective contribution of genetic and environmental factors. This study aims to investigate general distress as a mediator and cognitive/emotional control as a moderator in the stress–sleep relationship and estimate the influence of gene and environment in this mechanism using a national representative sample. Participants 1,255 middle-aged and elderly Americans and a subset of 296 twins. Methods The Pittsburgh Sleep Quality Index, the Perceived Stress Scale, the Mood and Anxiety Symptom Questionnaire and the Self-Control Scale assessed sleep quality, perceived stress, general distress, and emotional/cognitive control. Structural equation modeling was used to test the mediating and moderating effect. ACE models on MZ and DZ twins were used to separate the contribution of genetic and environmental factors. Finally, a co-twin design was nested in the SEM to control for the genetic and familial confounds in the stress–sleep relationship. Results General distress mediated the relationship between stress and sleep while emotional/cognitive control buffered the impact of stress on general distress. 7.69% of the variance in sleep quality was explained by genetic and familial factors and 8.26% was explained by individual-specific factors. Emotional/cognitive control only moderated the individual-specific association between stress and sleep. Conclusions Gene/family factors and individual factors explained an equivalent proportion of the stress–sleep relationship. The genetic and familial association between stress and sleep is more robust, whereas the individual-specific association can be buffered by regulation strategies.

Heritability of Age at Menarche in South Korean Female Twins.

Genetic and environmental influences on age at menarche (AAM) have rarely been examined in Asian females. This study aimed to investigate the heritability of AAM in South Korean female twins. The AAM data from 1370 female twins (933 monozygotic [MZ] twins, 294 dizygotic [DZ] twins and 160 female members of opposite-sex DZ twins) born between 1988 and 2001 were analyzed. The age of the sample at the time of the assessment ranged from 16 to 28 years with a mean of 19.3 (SD = 2.2) years. The mean AAM in the total sample was 12.49 (SD = 1.41) years. Although the mean AAM decreased with increasing birth years, it levelled off in birth years 2000-2001. Maximum likelihood MZ and DZ twin correlations were 0.72 [95% CI (0.67, 0.76)] and 0.35 [95% CI (0.19, 0.50)], respectively. The results of model-fitting analysis indicated that the additive genetic and individual-specific environmental effects were 72% [95% CI (67%, 76%)] and 28% [95% CI (24%, 33%)], respectively. Neither nonadditive genetic nor shared environmental effects were significant.

Evidence for type-specific DNA methylation patterns in epilepsy: a discordant monozygotic twin approach.

Aim: Epilepsy is a common neurological disorder characterized by recurrent seizures. We performed epigenetic analyses between and within 15monozygotic (MZ) twin pairs discordant for focal or generalized epilepsy. Methods: DNA methylation analysis was performed using Illumina Infinium MethylationEPIC arrays, in blood and buccal samples. Results: Differentially methylated regions between epilepsy types associated with PM20D1 and GFPT2 genes in both tissues. Within MZ discordant twin pairs, differentially methylated regions associated with OTX1 and ARID5B genes for generalized epilepsy and TTC39C and DLX5 genes for focal epilepsy. Conclusion: This is the first epigenome-wide association study, utilizing the discordant MZ co-twin model, to deepen our understanding of the neurobiology of epilepsy.

Salience network connectivity is reduced by a meal and influenced by genetic background and hypothalamic gliosis.

Background/Objectives:The salience network (SN) comprises brain regions that evaluate cues in the external environment in light of internal signals. We examined the SN response to meal intake and potential genetic and acquired influences on SN function.Subjects/Methods:Monozygotic (MZ; 40 pairs) and dizygotic (15 pairs) twins had body composition and plasma metabolic profile evaluated (glucose, insulin, leptin, ghrelin and GLP-1). Twins underwent resting-state functional magnetic resonance imaging (fMRI) scans before and after a standardized meal. The strength of SN connectivity was analyzed pre- and post-meal and the percentage change elicited by a meal was calculated. A multi-echo T2 MRI scan measured T2 relaxation time, a radiologic index of gliosis, in the mediobasal hypothalamus (MBH) and control regions. Statistical approaches included intraclass correlations (ICC) to investigate genetic influences and within-pair analyses to exclude genetic confounders.Results:SN connectivity was reduced by meal ingestion (β=−0.20; P<0.001). Inherited influences on both pre- and post-meal connectivity were present (ICC MZ twins 26%, P<0.05 and 47%, P<0.001, respectively), but not percentage change in response to the meal. SN connectivity in response to a meal did not differ between participants with obesity and of normal weight (χ2(1)=0.93; P=0.33). However, when participants were classified as having high or low signs of MBH gliosis, the high MBH gliosis group failed to reduce the connectivity in response to a meal (z=−1.32; P=0.19). Excluding genetic confounders, the percentage change in SN connectivity by a meal correlated to body fat percentage (r=0.24; P<0.01).Conclusions:SN connectivity was reduced by a meal, indicating potential participation of the SN in control of feeding. The strength of SN connectivity is inherited, but the degree to which SN connectivity is reduced by eating appears to be influenced by adiposity and the presence of hypothalamic gliosis.

A Behavioral Genetic Analysis of the Cooccurrence Between Psychopathic Personality Traits and Criminal Behavior

A developed line of research has found that psychopathic personality traits and criminal behavior are correlated with one another. Although there is little question about the association between psychopathic personality traits and criminal behavior, what remains less clear is whether psychopathic traits exert a direct effect on criminal behavior. An alternative possibility is that previously unmeasured genetic and shared environmental factors account for much of the association between the two. Understanding the extent to which genetic and environmental factors influence the covariance between psychopathic personality traits and criminal behavior can further our understanding of individual differences in propensity to engage in antisocial behavior. The current study analyzes 872 twins (MZ twins = 352, DZ twins = 520) from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine the magnitude of genetic and environmental effects on the covariation between psychopathic personality and criminal behavior. Results from bivariate behavioral genetic analyses revealed that the correlation between psychopathic personality traits and criminal behavior was accounted for by common additive genetic (58%) and nonshared environmental (42%) influences. Fixed-effect linear regression models, however, suggested that psychopathic personality traits were not significantly associated with criminal behavior once common genetic and environmental influences were taken into account.

Diagnosing Zygosity in Giant Panda Twins Using Short Tandem Repeats.

The giant panda, native to mountains of south-west China, is one of the world's rarest bear species and is subject to considerable conservation effort. In captivity, the proportion of twins accounts for 54% of the total number of births. To date, little is known about zygosity in panda populations - specifically, the proportion of monozygotic and dizygotic twins. In this study, we used 10 microsatellite markers for reliable zygosity testing, and the probability of monozygotic twins was 99.963% when all 10 markers were concordant. Out of 43 studied twin pairs, no MZ twins were found, indicating that there may be no identical panda twins (or the incidence is very low). We speculate that the fertilized eggs of giant pandas do not have the capability to split into two identical embryos, or that this ability is very poor, which is likely due to delayed implantation that is common in bear species. The results of this study deepen our understanding of giant panda breeding, yield insight into panda twins' likely mechanism of formation, and reduce the uncertainty of individual identity in wild population surveys.

Pairs of Genetically Unrelated Look-Alikes

Relationships of physical resemblance to personality similarity and social affiliation have generated considerable discussion among behavioral science researchers. A "twin-like" experimental design (involving genetically unrelated look-alikes, U-LAs) explores associations among resemblance in appearance, the Big Five personality traits, self-esteem, and social attraction within an evolutionary framework. The Personality for Professionals Inventory (PfPI), NEO/NEO-FFI-3, Rosenberg Self-Esteem Scale, and a Social Relationship Survey were variously completed by 45U-LA pairs, identified from the "I'm Not a Look-Alike" project, Mentorn Media, and personal referrals. The mean U-LA intraclass correlations were negligible for all Big Five personality traits on the PfPI and NEO/NEO-FFI-3 (ri= -.02 and - .04, respectively). In contrast, mean ri values of .53 and .15 for monozygotic (MZA) and dizygotic (DZA) reared-apart twins, respectively, have been reported for these personality measures. The U-LA self-esteem correlation (ri= -.18) was also below the correlations reported for MZ and DZ reared-together twins (ri = .31 and .13, respectively). Finally, far fewer U-LAs expressed close social relationships (20%) than MZA (80%) and DZA (65%) twins. The present study extends earlier findings indicating that appearance is not meaningfully related to personality similarity and social relatedness. The criticism that MZ twins are alike in personality because their matched looks invite similar treatment by others is refuted. A more judicious interpretation is reactive genotype-environment correlation, namely that MZ twins' similar personalities evoke similar reactions from others. MZ twins' close social relations most likely derive from their perceptions of genetically based within-pair similarities that are lacking in U-LAs.

Clinical Characteristics, Life Adversities and Personality Traits in Monozygotic Twins With, at Risk of and Without Affective Disorders.

Background: Affective disorders have a long-term impact on psychiatric health and are caused by multiple interacting factors including familial risk, childhood adversity, life events and personality traits.Methods: In this study, monozygotic twins (MZ) at familial risk (indexed by affective disorder in their co-twin; high-risk group), affected MZ twins (indexed by a diagnosis with affective disorder) and MZ twins with no family history of affective disorder (low-risk group) were identified through cross-linking of nation-wide Danish registers. In total, 204 MZ twins were included and psychopathology, personality traits and life adversity were evaluated by semi-structured interviews and questionnaires.Results: Affected MZ twins presented with more subclinical affective symptoms and were functionally impaired as evidenced by higher unemployment rates and reduced functional status. The affected and the high-risk groups reported more childhood adversity and had experienced more stressful life events than the low-risk group. A direct comparison within the discordant twin pairs showed that the high-risk twins presented fewer affective symptoms, better functional status, more extraversion and lower neuroticism scores than their affected co-twins although they had equal levels of life adversity as their affected co-twins.Conclusion: These findings add to the evidence indicating that patients experience higher neuroticism, persistent subclinical symptoms and reduced socio-occupational function after affective episodes. Additionally, neuroticism and extraversion seem capable of moderating the sensitivity to exposure from the environment.

Risk of Islet and Celiac Autoimmunity in Cotwins of Probands with Type 1 Diabetes

Concordance for persistent islet autoimmunity (IA) and type 1 diabetes (T1D) in monozygotic twins (MZ) after one twin is diagnosed has been highly variable (30-70%), while risk for development of IA in dizygotic twins (DZ) is thought to be similar to non-twin siblings. Since 1995, the Twin Family Study at the Barbara Davis Center has followed 336 twins (168 twin probands diagnosed with T1D and 168 cotwins) with a median follow-up of 14 years (ICR:10-18 years). Zygosity testing confirmed a total of 80 MZ pairs and 88 DZ pairs. Cotwins were followed for the development of IA and celiac autoimmunity (CDA). In MZ cotwins, cumulative incidence for IA was 14% by age 20 and 63% by age 45, while development of CDA was 10% by 20 years. Development of IA and CDA by age 20 was 9.2% and 12.3% in DZ cotwins respectively, with development of IA reaching 70% by age 30 (Figure). In Cox proportional hazards models, only the proband’s age at diagnosis, but not sex, HLA-DR3 nor DR4 were associated with time to IA and CDA in cotwins. In MZ twins, younger age of the proband was associated with an increased hazard ratio (HR) for both IA and CDA, while younger age in DZ twins was associated with an increased HR for IA only. In conclusion, CDA risk does not appear to increase after age 15. With long term follow-up, cumulative incidence for IA is high in DZ twins, similar to MZ twins, suggesting a role of possible early environmental factors shared by T1D-discordant cotwins. Disclosure T.M. Triolo: None. A.R. Fouts: None. L. Pyle: None. L. Yu: None. P. Gottlieb: Advisory Panel; Self; Bristol-Myers Squibb Company. Research Support; Self; Caladrius Biosciences, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; ImmunoMolecular Therapeutics. Consultant; Self; Kamada. Research Support; Self; JDRF, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., MacroGenics, Inc., Pfizer Inc.. Advisory Panel; Self; Viacyte, Inc.. Research Support; Self; GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.. A. Steck: None.

Monozygotic twin differences in school performance are stable and systematic.

School performance is one of the most stable and heritable psychological characteristics. Notwithstanding, monozygotic twins (MZ), who have identical genotypes, differ in school performance. These MZ differences result from non-shared environments that do not contribute to the similarity within twin pairs. Because to date few non-shared environmental factors have been reliably associated with MZ differences in school performance, they are thought to be idiosyncratic and due to chance, suggesting that the effect of non-shared environments on MZ differences are age- and trait-specific. In a sample of 2768 MZ twin pairs, we found first that MZ differences in school performance were moderately stable from age 12 through 16, with differences at the ages 12 and 14 accounting for 20% of the variance in MZ differences at age 16. Second, MZ differences in school performance correlated positively with MZ differences across 16 learning-related variables, including measures of intelligence, personality and school attitudes, with the twin who scored higher on one also scoring higher on the other measures. Finally, MZ differences in the 16 learning-related variables accounted for 22% of the variance in MZ differences in school performance at age 16. These findings suggest that, unlike for other psychological domains, non-shared environmental factors affect school performance in systematic ways that have long-term and generalist influence. Our findings should motivate the search for non-shared environmental factors responsible for the stable and systematic effects on children's differences in school performance. A video abstract of this article can be viewed at: https://youtu.be/0bw2Fl_HGq0.

Heritability of myopia and its relation with GDJ2 and RASGRF1 genes in Lithuania

BackgroundThis study aimed to assess heritability of myopia in Lithuania and evaluate both genes GJD2 (Gap Junction Protein, Delta 2) and RASGRF1 (RAS protein-specific guanine nucleotide-releasing factor 1) relation with myopia.MethodsIn this study Lithuanian twin population aged between 18 and 40 (n = 460) were examined. Single-nucleotide polymorphisms of the RASGRF1 (rs8027411) and GJD2 (rs634990) genes were assessed by real-time polymerase chain reaction method.ResultsIntrapair correlations for spherical equivalent in all twin pairs were significantly higher in MZ twin pairs r = 0.539 (p < 0.001, 95% CI 0.353–0.684) than in DZ twin pairs r = 0.203 (p < 0.01, 95% CI 0.0633–0.442) in myopia group. Correlations for spherical equivalent in emmetropia group were not significant in MZ twin pairs r = 0.091 (p > 0.05, 95% CI -0.215-0.381) and in DZ twin pairs r = − 0.220 (p > 0.05, 95% CI -0.587-0.222). The odds ratio (95% CI) were 2.7 (1.018–7.460) for combinations of genotypes of rs634990 CC and rs8027411 GT (p = 0.046).ConclusionsOur studies have shown that the heritability of myopia makes 67.2% in Lithuania. Persons with combinations of genotypes rs634990 CC and rs8027411 GT have 2.7 times higher odds to have myopia.

Is the Association Between Obesity and Hip Osteoarthritis Surgery Explained by Familial Confounding?

Familial confounding is confounding due to genetics or environmental exposures shared by family members. We aimed to study whether familial confounding explains the association between body mass index (BMI) and severe hip osteoarthritis (OA). We linked data from the Norwegian Arthroplasty Registry with the Norwegian Twin Registry on the National ID-number in 2014, generating a population-based prospective cohort study of same-sex twins born between 1915 and 1960 (53.4% females). BMI was calculated from self-reported height/weight. The outcome was incident hip arthroplasty due to OA (follow-up time, 1987-2014; 424 914 person-years). We performed sex-specific co-twin control analyses of dizygotic (N = 5,226) and monozygotic (MZ, N = 3,803) twin pairs using Cox regression models and explored reasons for any familial confounding using bivariate twin models. The mean (SD) BMI was 22.6 (2.96), peak lifetime BMI 25.6 (2.61), and N = 614 had hip surgery due to OA. In cohort analyses, BMI was associated with hip OA for women and men (hazard ratio [HR] = 1.09, 95% confidence intervals [CIs] = 1.06 to 1.11 and HR = 1.08, 95% CI = 1.04 to 1.12, respectively). When adjusting for familial confounding within MZ twins, the association got stronger for women (HR = 1.19; 95% CI = 1.05 to 1.36) but weaker for men (HR = 0.93; 95% CI = 0.75 to 1.16). There was no genetic overlap between BMI and hip OA, yet the familial confounding in men provides suggestive evidence that the association could be explained by shared environmental factors. The association between BMI and hip OA may be explained by familial confounding for men. For women, there was no evidence for familial confounding, consistent with a causal association. See video abstract at, http://links.lww.com/EDE/B336.