A discordant twin gestation, in which one fetus is significantly growth restricted, compared to the other normal twin, is a unique model that can be used to elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. In many model systems, placental transcription factor genes regulate fetal growth. Transcription factors regulate growth through their activation or repression of downstream target genes that mediate important cell functions. The objective of this study was to determine the expression of the placental HLX homeobox gene transcription factor and its downstream target genes in dizygotic twins with growth discordance. In this cross-sectional study, HLX and its downstream target genes’ retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C) expression levels were determined in placentae obtained from dichorionic diamniotic twin pregnancies (n = 23) where one of the twins was growth restricted. Fetal growth restriction (FGR) was defined as small for gestational age with abnormal umbilical artery Doppler indices when compared with the normal control co-twin. Homeobox gene HLX expression was significantly decreased at both the mRNA and protein levels in FGR twin placentae compared with the normal control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were also significantly decreased and increased, respectively, at both the mRNA and protein levels in FGR twin placentae compared with normal control co-twin placentae (p < .05). Together, these observations suggest an important association between HLX transcription factor expression and abnormal human placental development in discordant twin pregnancies.

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

The management of twin pregnancies discordant for trisomy 21 is dependent on the gestation at diagnosis, chorionicity, and parental preference. Our experience with the management of 15 cases in 1,839 twin pregnancies over a 12-year period is described. Selective termination is not always associated with a successful outcome for the normal co-twin. Two of the three monochorionic twin pregnancies affected by trisomy 21 were discordant. Amniocentesis should be strongly considered rather than chorionic villus sampling in monochorionic twin pregnancies. Pregnancies that continue with a trisomy 21 affected fetus are at risk of polyhydramnios and premature labor.

The purpose of this study was to examine potential biases in family history reports of problem gambling and gambling frequency. Same-sex twin pairs discordant for a history of problem (n = 230 pairs) and pathological gambling (n = 48 pairs) and for three indexes of gambling frequency (ever gambling, monthly gambling, and weekly gambling; n = 44–517 pairs) were identified from a large Australian national twin study. The problem gambling affected twin was significantly more likely to endorse paternal problem gambling than the problem gambling unaffected cotwin (OR = 5.5), and similar findings were obtained for family history reports of gambling frequency (OR = 2.0–2.8). These results could not be explained by differences between the discordant pairs in whether they had spent time gambling with the parents; there was no association between a history of problem, monthly or weekly gambling and having gambled with the parents among discordant twin pairs. The results of this study suggest that relying solely on family history assessments of disordered gambling and gambling involvement can lead to incorrect estimates of the strength of the family history effect.

The current article examines the assumptions of the MZ co-twin control method that has been applied in attempts to gain more accurate estimates of the returns to education by naturally ‘controlling’ for individual differences on which MZ twins are matched. The current study examined 1738 MZ and 926 DZ twins from Minnesota, including 133 pairs of MZ and 101 pairs of DZ twins discordant for university attendance. They were assessed prospectively on personality, intelligence, GPA, and academic motivation; a subset also has reported income at age 29. MZ twins discordant for university attendance differed significantly and prospectively on verbal IQ, personality traits, and GPA. While MZ co-twin control studies can provide more accurate estimates of the returns to education than analyses of single individuals, these studies do not entirely obviate the need to control for differences between university students and non-students that predate university attendance and might account for income differentials and even non-monetary outcomes.