Discordant Twins Research Articles

White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and linked with risk factors. A twin study

Low mitochondrial DNA copy number (mtDNA CN) has been associated with e.g. cancer, cardiovascular and autoimmune diseases. We aimed to study a potential association between mtDNA CN and rheumatoid arthritis (RA).The relative quantity of mitochondrial DNA compared to nuclear DNA was measured in peripheral white blood cells from 149 RA affected twin pairs and 1321 non-affected twin pairs. Multiple regression analysis including RA discordant twin pairs was performed in order to separate specific effects of RA and familial RA predisposition using non-RA affected twin pairs as reference group. In addition, we performed a twin pair level analysis including only RA discordant twin pairs evaluating the effect of cell type, auto antibodies and RA genetic risk factors.Both the RA twins and their non-affected co-twins had significantly lower mtDNA CN than non-affected twins (−28.7 and −23.1 mtDNA CN, respectively). Adjusting for cell count attenuated these differences (−23.1 mtDNA CN and −20.1 mtDNA CN respectively). Within RA discordant twin pairs PTPN22(T) positive RA twins had a significantly lower amount than their co-twins (−16.3 mtDNA CN). PTPN22(T) had no effect among twins from non-affected twin pairs.MtDNA CN is significantly lower in persons with established RA and in predisposed non-affected RA co-twins suggesting that mitochondrial variation may be involved in the RA disease pathways. Our results also suggest that the RA associated genetic risk factor, PTPN22(T), further decreases the mtDNA CN, but only in carriers with established RA.

Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins

BackgroundRheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs.MethodsGenome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.ResultsWe have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.ConclusionsThrough genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.

Abstract 090: Does Dietary Sodium Contribute to the Discordance in Blood Pressures among Monozygotic Twins?

Background: Dietary sodium (Na) and central adiposity are considered important risk factors for hypertension (HTN). Blood pressure (BP) levels are discordant among 40-50% of monozygotic (MZ) twin pairs. One prior study of MZ twins using questionnaires reported that hypertensive (HT) MZ twins differed in their intake of meat and milk. However, none of the previous studies have evaluated the impact of Na intake on BP in MZ twins. Methods: Eighty-eight pairs of MZ twins were enrolled from Milwaukee, WI and Michigan State University Twin Registry, East Lansing, MI (age- 44 ± 9 years, 63% women, and 96% Caucasian). BPs (measured in triplicate and averaged) and anthropometrics were measured. Na intake was calculated using Block Sodium Screener. Twin pairs were considered concordant or discordant based on systolic (SBP) or diastolic BP (DBP) difference of 10 mm Hg between co-twins, off BP medications Results: Thirty-seven twin pairs were discordant in their BP levels. Mean (± SD, mm Hg) SBP/DBPs among concordant and discordant twins were 120 ± 12 / 77 ± 9 and 131 ± 18 / 81 ± 10 respectively. Mean differences in SBP/DBP among concordant and discordant twins were 5 ± 7 / 4 ± 4 and 14 ± 8 / 10 ± 6 respectively. Discordant twins as a group had higher waist circumference (WC) compared to concordant twins (p<0.05), but with no differences in BMI or Na intake. However, among the discordant twin pairs, the co-twin with higher BPs (138 ± 18 / 85 ± 9) had higher dietary salt intakes (3900 ± 1437 vs. 3261 ± 1058 mg/d) and higher WC (105 ± 15 vs. 98 ± 18 cm) (p=0.02) compared to their co-twin with lower BPs (121 ± 16 / 77 ± 9). The average Na intake among the concordant twins was 3443 ± 1189 mg/day. Differences in Na intake among discordant co-twins remained statistically significant after adjustment for age, gender, BMI, WC, and waist-to-hip ratio. Conclusions: Higher Na intake is associated with higher BPs among MZ twins with discordant BPs. Differences in Na intakes were significant independent of central adiposity indicating significant Na sensitivity in discordant MZ twin pairs. The effect of ~500mg less Na intake/day in resulting in lower BPs in genetically identical individuals, suggests that modest decreases in Na-intake in Na-sensitive individuals may be sufficient to see the desired effect on BP levels.

Pregnancy and perinatal outcomes of first-trimester crown-rump length discordance in dichorionic twin pregnancies after in vitro fertilization

To evaluate the association between first- trimester crown-rump length discordance and adverse pregnancy and perinatal outcomes in dichorionic twin pregnancies. This was a retrospective cohort study of women with dichorionic twin pregnancies after in vitro fertilization (IVF) at our fertility center with two live fetus scanned between 6+5 and 8 weeks’ gestation during the period 1st January 2015 and 1st January 2017. Study groups were defined by the presence or absence of ≥20% crown-rump length (CRL) discordance at the first-trimester ultrasound scans. Pregnancy outcomes including spontaneous abortion, stillbirth and live birth were compared between discordant and concordant twin pregnancies. Perinatal outcomes (preterm delivery, [PTD], low birth weight [LBW], very low birth weight [VLBW], birthweight discordant, neonatal death and admission in neonate intensive care unit [NICU]) were also assessed. Singleton live deliveries and twin deliveries were analyzed separately. Moreover, fetal anomalies were also evaluated. During the study period we identified 1687 dichorionic twin pregnancies on first-trimester ultrasound, of which1504 met the inclusion criteria. Of the 1504 dichorionic twin pregnancies included, 129 (8.58%) patients were identified as having CRL discordance of at least 20%. CRL discordant twin were more likely to end in one fetal loss before 12 weeks’ gestation (Relative risk= 15.073,95% confidence interval, 10.128-22.431) than were concordant dichrionic twin pregnancies. Discordant twin pregnancies with twin deliveries were at significant higher risk of birthweight discordance (Relative risk=2.192,95% confidence interval, 1.054-4.558). There was no significant difference in perinatal outcomes including PTD, LBW, VLBW, neonatal death and admission to NICU in singleton or twin deliveries. No fetal anomalies were observed in discordant twin pregnancies. Dichorionic twin pregnancies were at increased risk for one fetal loss prior to 12 weeks’ gestation and birthweight discordance, but were not associated with adverse perinatal outcomes and fetal anomalies.

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.

Epstein-Barr virus load is higher in long-term Hodgkin lymphoma survivors compared to their unaffected twins and unrelated controls.

Epstein-Barr virus load is higher in long-term Hodgkin lymphoma survivors compared to their unaffected twins and unrelated controls.

Epigenetic Basis of Twin Discordance in Diseases: Future Benefits

Monozygotic twins share the same genotype since they are derived from the same zygote. However, monozygotic (MZ) twin siblings frequently present many phenotypic differences, such as their susceptibilities to diseases. These isogenic individuals are not entirely identical. They exhibit phenotypic incompatibility for many features, from birth weight to complex diseases. Recently, several studies have been published showing that phenotypic differences, especially in MZ twins, are being induced from prenatal period to life-long epigenetic differences. Epigenetic studies on twins have a great potential to contribute to our understanding of complex diseases, such as cancer, autoimmune disorders, psychiatric disorders and neurological diseases. Since MZ twins are genetic clones (genetically identical), they are considered as perfect models for studying the role of environmental factors as determinants of complex diseases and phenotypes. In this review, a number of intrauterine effects and genetic mechanisms that may affect phenotypic, genotypic, and epigenetic differences between MZ twins were described and effects of epigenetic mechanisms on complex diseases were mentioned. Further work on epigenetic changes in diseases using incompatible MZ twin models, would lead to new developments in medical therapies.

Femoral-facial syndrome: A review of the literature and 14 additional patients including a monozygotic discordant twin pair.

Femoral-facial syndrome (FFS, OMIM 134780), also known as femoral hypoplasia-unusual face syndrome, is a rare sporadic syndrome associated with maternal diabetes, and comprising femoral hypoplasia/agenesis and a distinct facies characterized by micrognathia, cleft palate, and other minor dysmorphisms. The evaluation of 14 unpublished Brazilian patients, prompted us to make an extensive literature review comparing both sets of data. From 120 previously reported individuals with FFS, 66 were excluded due to: not meeting the inclusion criteria (n = 21); not providing sufficient data to ascertain the diagnosis (n = 29); were better assigned to another diagnosis (n = 3); and, being fetuses of the second trimester (n = 13) due to the obvious difficult to confirm a typical facies. Clinical-radiological and family information from 54 typical patients were collected and compared with the 14 new Brazilian patients. The comparison between the two sets of patients did not show any relevant differences. Femoral involvement was most frequently hypoplasia, observed in 91.2% of patients, and the typical facies was characterized by micrognathia (97%), cleft palate (61.8%), and minor dysmorphisms (frontal bossing 63.6%, short nose 91.7%, long philtrum 94.9%, and thin upper lip 92.3%). Clubfoot (55.9%) was commonly observed. Other observed findings may be part of FFS or may be simply concurrent anomalies since maternal diabetes is a common risk factor. While maternal diabetes was the only common feature observed during pregnancy (50.8%), no evidence for a monogenic basis was found. Moreover, a monozygotic discordant twin pair was described reinforcing the absence of a major genetic factor associated with FFS.

Discordant congenital Zika virus infection in dizygotic twins: a case report

Background: Discordant clinical outcomes in congenital infectious disorders have been described, such as in Cytomegalovirus, toxoplasmosis and HIV infection, most of then in dizygotic twin pregnancies. In Brazil, since 2015, more than 2800 cases of congenital Zika infection (CZI) were confirmed. To date, three cases of discordant CZI infection in twins were reported, one case in monozygotic pregnancy and two cases in dizygotic twin pregnancies. Methods & Materials: Here, we describe a case report with the clinical presentation of discordant twin siblings, one with microcephaly

Handedness and the Corpus Callosum: A Review and Further Analyses of Discordant Twins

Handedness effects with respect to regional corpus callosum (CC) anatomy remain open to question. Midsagittal CC tracings were obtained from structural MRIs in 21 female monozygotic twin pairs with discordant handedness (MZHd). The CC was divided into 99 percentile widths which were grouped into seven regions based on Denenberg’s (1989, 1991b) factor analysis. Results showed that left handed (LH) twins had significantly larger regional widths in CC region W22–39 compared to right handed (RH) twins, an effect present in 19/21 MZHd pairs. Cross-study analyses revealed CC W22–39 to have the highest variation across female singletons (Cowell et al., 1992, 1993). In the adjacent genu region (W3–18), CC size did not differ between RH and LH twins. However, when twins were reclassified according to handedness direction and consistency to form consistent RH, non-consistent RH, consistent LH and non-consistent LH groups, patterns of CC size in W3–18 closely matched those of singleton women (Cowell et al., 1993). Namely, CC W3–18 was larger in consistent compared to non-consistent RHs. Results support a claim that CC region W22–39, interconnecting premotor cortex in females, provides for environmentally influenced components of handedness, given the difference within MZHd twin pairs. By contrast, CC W3–18, connecting prefrontal cortex, was sensitive to direction and consistency of handedness, both in twins and singletons, a result consistent with combined genetic and environmental effects. Findings highlight the significance of MZHd twin studies in elucidating the developmental mechanisms underpinning structure–function asymmetry, cortical interconnectivity and neurodevelopmental bases of left hand preference.

Association of current and former smoking with body mass index: A study of smoking discordant twin pairs from 21 twin cohorts

BackgroundSmokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background.Methods and findingsThe international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18–69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade.ConclusionsSmoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2.

Whole-genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes.

Orofacial clefts (OFCs) are common and etiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole-genome sequencing. One co-twin (MZ-1) presented with nonsyndromic bilateral cleft lip and palate; the other co-twin (MZ-2) had nonsyndromic bilateral cleft lip and unilateral left-sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole-genome sequencing, respectively. Morphologically, MZ-1 had a smaller vertical mandibular height, compared to MZ-2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harbored rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. The observed differences between MZ-1 and MZ-2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development.

Differences in the Expression of TLR-2, NOD2, and NF-\u03baB in Placenta Between Twins

Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-κB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic–dichorionic and monoamniotic–dichorionic twins. Monoamniotic–monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-κB, NOD2 and TLR-2 between twins. In case of twin-to-twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment.

Research on oral microbiota of monozygotic twins with discordant caries experience - in vitro and in vivo study

Oral microbiome is potentially correlated with many diseases, such as dental caries, periodontitis, oral cancer and some systemic diseases. Twin model, as an effective method for studying human microbiota, is widely used in research of relationship between oral microbiota and dental caries. However, there were few researches focusing on caries discordant twins. In this study, in vitro assays were conducted combined with 16S rRNA sequencing analysis on oral microbiota sampled from twins who presented discordant caries experience and mice model was developed as well. Results showed that oral microbiota from caries-active twin possessed higher metabolic activity and produced more lactic production. 16S rRNA sequencing analysis showed that more than 80% of family taxa could be transferred into gnotobiotic-mice. Key caries-associated genera were significantly different between twins and the same difference in genus level could be found in mice as well (p < 0.05). This study suggested that oral microbiota of twins could be distinguished from each other despite the similarities in genetic make-up, living environment, and lifestyle. The difference in microbiota was applied to develop a mice model which may facilitate the investigation of core microbiota of dental caries.

Nuchal Fold Thickness (NFT) in Male versus Female Fetus in Gender Discordant Twins [17E

INTRODUCTION: To evaluate second trimester nuchal fold thickness (NFT) in male versus female fetuses in gender-discordant dizygotic twin pregnancies. METHODS: Case control study of dizygotic twin pregnancies receiving second trimester fetal nuchal fold measurements identified from a search of ultrasound and cytogenetic databases. Structurally normal fetuses that delivered beyond 30 weeks of gestational age without known chromosomal aberrations were included. NFT was compared in male versus female fetuses using paired t-test. RESULTS: 220 dizygotic twin pregnancies were included. Male fetuses had a higher mean NFT as compared to female fetuses in the entire cohort (3.7 mm in males versus 3.5 mm in females, p &lt; 0.0001, 95% CI 0.3-0.1). Data was stratified based on gestational age. There was a gradual increase in NFT with an increase in gestational age. Male fetuses had a higher NFT through all the gestational ages. CONCLUSION: Male fetuses had a higher mean NFT as compared to female fetuses in gender-discordant dizygotic twin pregnancies.

The relationship between subjective well-being and mortality within discordant twin pairs from two independent samples.

Prior research has shown robust associations between greater subjective well-being (SWB) and reduced mortality. Whether this observed association is causal in nature or due instead to confounding genetic or environmental factors affecting both SWB and mortality is not well understood. We used a combined sample of 6,802 twins drawn from two cohorts: the Longitudinal Study of Middle-Aged Danish Twins (MADT; N = 2,815, baseline age between 45 and 69 years, M = 56.8, SD = 6.4) and the Longitudinal Study of Aging Danish Twins (LSADT; N = 3,987, baseline age between 70 and 97 years, M = 76.6, SD = 4.9). The relationship between SWB, encompassing measures of life satisfaction and affect, and all-cause mortality was evaluated using survival analyses at both the individual level and within twin pairs. Twin difference analyses were completed within 1,053 monozygotic (MZ) twin pairs and 1,143 dizygotic (DZ) twin pairs to control for genetic and shared environmental confounding. As expected, the individual-level results showed that higher levels of SWB were associated with reduced mortality: affect hazard ratio (HR) = .90, 95% confidence interval (CI) [.87, .94]; life satisfaction HR = .88, 95% CI [.84, .92]. The effect of SWB on reduced mortality remained significant within both MZ and DZ pairs, suggesting that the association is independent of genetic and nonshared environmental confounding factors. These findings, which generalized across both younger (MADT) and older (LSADT) cohorts of adults, remained significant when accounting for demographic factors, physical health, and cognitive functioning. (PsycINFO Database Record

Identification of somatic mutations in monozygotic twins discordant for psychiatric disorders

Monozygotic twins are assumed to have identical genomes. Based on this assumption, phenotypic discordance in monozygotic twins has been previously attributed to environmental factors. However, recent genomic studies have identified characteristic somatic mutations in monozygotic twins discordant for Darier disease, Van der Woude syndrome, and Dravet syndrome. Here, we explored somatic mutations in four pairs of monozygotic twins discordant for schizophrenia or delusional disorder. We analyzed whole exome sequence data obtained from blood samples and identified seven somatic mutations in one twin pair discordant for delusional disorder. All seven of these mutations were validated by independent amplicon sequencing, and five of them were further validated by pyrosequencing. One somatic mutation in the patient with delusional disorder showed a missense variant in ABCC9 with an allele fraction of 7.32%. Although an association between the somatic mutations and phenotypic discordance could not be established conclusively in this study, our results suggest that somatic mutations in monozygotic twins may contribute to the development of psychiatric disorders, and can serve as high-priority candidates for genetic studies.

Association between obesity and DNA methylation among the 7-16 year-old twins

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.

Genetic and epigenetic etiology of autoimmune diseases: lessons from twin studies

Twin studies have been considered as strong approaches in determining the cause of complex diseases with regard to identifying the involvement of multiple genes, single genes, environmental factors, and a possible relation between genetics and the environment. The concordance observed among monozygotic (MZ) twins suggests the involvement of genetic factors. Nonetheless, MZ twins demonstrate a rate of discordance in different characteristics, like proneness towards diseases, despite virtually identical genetic backgrounds. Discordance has been suggestive of the involvement of the environment alongside genetic factors. As a result, a bulk of studies has supported the hypothesis that environmental factors can impress the epigenetic construction and, therefore, influence disease susceptibility. Twin studies yield data about clinical courses and outcomes of disease, in addition to knowledge of genetics, epigenetics, environmental factors, and risk of disease development. To date, genome-wide association studies (GWASs) have reported that genomic variants are responsible for only a number of cases of autoimmunity in twins and have been unable to explain the disease discordance among MZ twins. With respect to the exploration of epigenetic mechanisms in autoimmunity, discordant MZ twins have been attractive models and have contributed remarkably. It is essential for future studies to evaluate the genetic variants as well as epigenetic changes in large twin populations. The current review discusses the genetic and epigenetic lessons obtained from studies of twin cases.

Gender nonconformity of identical twins with discordant sexual orientations: Evidence from childhood photographs.

Childhood gender nonconformity (femininity in males, masculinity in females) predicts a nonstraight (gay, lesbian, or bisexual) sexual orientation in adulthood. In previous work, nonstraight twins reported more childhood gender nonconformity than their genetically identical, but straight, cotwins. However, self-reports could be biased. We therefore assessed gender nonconformity via ratings of photographs from childhood and adulthood. These ratings came from independent observers naïve to study hypotheses. Identical twins with discordant sexual orientations (24 male pairs, 32 female pairs) visibly differed in their gender nonconformity from mid-childhood, with higher levels of gender nonconformity observed in the nonstraight twins. This difference was smaller than the analogous difference between identical twins who were concordant straight (4 male pairs, 11 female pairs) and identical twins unrelated to them who were concordant nonstraight (19 male pairs, 8 female pairs). Further, twins in discordant pairs correlated in their observer-rated gender nonconformity. Nongenetic factors likely differentiated the discordant twins' gender-related characteristics in childhood, but shared influences made them similar in some respects. We further tested how recall of past rejection from others related to gender nonconformity. Rejection generally increased with gender nonconformity, but this effect varied by the twins' sexual orientation. (PsycINFO Database Record