Concordant Monozygotic Twin Pairs Research Articles

A Twin Study of Perthes Disease.

Legg-Calvé-Perthes disease (LCPD) is an idiopathic avascular necrosis of the femoral head. Its etiology is poorly understood, although previous studies have implicated low birth weight and possible genetic determinants. The aim of this study was to identify potential birth weight and genetic associations with LCPD. We extracted all twin pairs from the Danish Twin Registry (DTR) in which at least 1 individual had LCPD. The DTR captures every twin pair born alive in Denmark, and those with LCPD were identified by using health record linkage. Probanwise concordance was calculated to describe the likelihood that any given individual had LCPD if their co-twin was also diagnosed. There were 81 twin pairs: 10 monozygotic, 51 dizygotic, and 20 unclassified (unknown zygosity [UZ]). There was no association between birth weight and being the affected co-twin. Four pairs (2 dizygotic and 2 UZ) were concordant for LCPD, which is greater than would be expected assuming no familial aggregation. There were no concordant monozygotic twin pairs. The overall probandwise concordance was 0.09 (95% confidence interval [CI]: 0.01-0.18): 0.00 for the monozygotic, 0.08 (95% CI: 0.00-0.18) for the dizygotic, and 0.18 (95% CI: 0.00-0.40) for the UZ twin pairs. This study found evidence of familial clustering in LCPD but did not show a genetic component. The absolute risk that a co-twin of an affected individual will develop LCPD is low, even in the case of monozygotic twin pairs.

Concordance rate of alopecia areata in identical twins supports both genetic and environmental factors

Concordance rate of alopecia areata in identical twins supports both genetic and environmental factors

Clinical characteristics of migraine concordant monozygotic twin pairs.

The aim of the study was to search for clinical differences between migraine with and without aura. From a population-based Finnish Twin Cohort we studied 51 migraine concordant monozygotic twin pairs. There were 20 pairs concordant for migraine with aura, 6 pairs concordant for migraine without aura and 12 "mixed" pairs. In the remaining 13 pairs the aura of at least 1 twin could not be classified. All 20 migraine with aura pairs were concordant for visual aura and 19 for moderate or severe headache while all 6 pairs with migraine without aura were concordant for headache duration of 4 to 24 h, moderate or severe headache and nausea. The 12 "mixed" pairs had more often unilateral and pulsating headache compared to both the migraine with or without aura pairs. Overall individual migraine with aura twins had more photophobia (P = 0.032) and the migraine without aura twins more nausea (P = 0.025). The difference between migraine with and without aura is not explained entirely by genetical factors: 12 genetically identical twin pairs were discordant for the aura. The headache phase in migraine with and without aura is very similar, but not identical. Probably there are several and different liability loci for the migraine aura and the migraine headache. The distribution of these several loci along with acquired factors will decide whether the phenotype is migraine with or without aura.

Gene expression analysis in absence epilepsy using a monozygotic twin design

To identify genes involved in idiopathic absence epilepsies by analyzing gene expression using a monozygotic (MZ) twin design. Genome-wide gene expression in lymphoblastoid cell lines (LCLs) was determined using microarrays derived from five discordant and four concordant MZ twin pairs with idiopathic absence epilepsies and five unaffected MZ twin pairs. Gene expression was analyzed using three strategies: discordant MZ twins were compared as matched pairs, MZ twins concordant for epilepsy were compared to control MZ twins, and a singleton design of affected versus unaffected MZ twin individuals was used irrespective of twin pairing. An overlapping gene list was generated from these analyses. Dysregulation of genes recognized from the microarray experiment was validated using quantitative real time PCR (qRT-PCR) in the twin sample and in an independent sample of 18 sporadic absence cases and 24 healthy controls. Sixty-five probe sets were identified from the three combined microarray analysis strategies. Sixteen genes were chosen for validation and nine of these genes confirmed by qRT-PCR in the twin sample. Differential expression for EGR1 (an immediate early gene) and RCN2 (coding for the calcium-binding protein Reticulocalbin 2) were reconfirmed by qRT-PCR in the independent sample. Using a unique sample of discordant MZ twins, our study identified genes with altered expression, which suggests novel mechanisms in idiopathic absence epilepsy. Dysregulation of EGR1 and RCN2 is implicated in idiopathic absence epilepsy.

Carcinoma in situ cervicis uteri and inheritance—A Danish twin study

Objective. To determine the relative environmental and genetic influence in the development of carcinoma in situ (CIS) cervicis uteri. Methods. Retrospective follow-up study with record linkage between The Danish Twin Register and The Danish Cancer Register. The study base comprises 27,004 female twins from 13,502 same-sex twin pairs. 5258 were monozygotic and 8244 dizygotic twin pairs. The statistic measurements are the coincidence ratio and the probandwise concordance rate in the two groups of twins with different zygosity. Results. 750 twins were diagnosed with CIS cervicis uteri. 291 monozygotic twins came from 275 pairs and 459 dizygotic twins came from 435 pairs. There were 16 concordant monozygotic twin pairs and 24 concordant dizygotic pairs. The probandwise concordance rate was 0.11 (0.06–0.16) in monozygotic twins and 0.10 (0.06–0.14) in dizygotic twins. Conclusion. A family clustering of CIS was demonstrated in both groups of zygosity. The probandwise concordance rate was equal in the monozygotic and the dizygotic groups, which means that genetic factors are not important in the development of the disease. However, a shared environment among twins plays a role in the development of CIS cervicis uteri.

Genetics of cluster headache: an update

Up to a few years ago, cluster headache (CH) was not thought to be an inherited disorder. However, several recent studies have suggested that genetic factors play a role in the disease. Genetic epidemiological surveys have shown that first–degree relatives of CH patients are more likely to have CH than the general population. CH has been reported in some concordant monozygotic twin pairs. At present, the type and the number of genes involved in the disease are still unclear. No mutation in the CACNA1A and NOS genes was found in CH patients. Recently, we have reported a significant association between the HCRTR2 gene and the disease. The purpose of this review is to describe recent advances in the genetics of CH.

Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics

Background & Aims: In 1988, we reported the first twin study in inflammatory bowel disease. The aim of the current study was to follow up these twins regarding new cases of inflammatory bowel disease and Crohn’s disease characteristics using the Vienna classification. Methods: The official Swedish population register and the cause of death register were used to search for the twins. All living patients were interviewed. Results: Three monozygotic twins earlier classified as healthy had been diagnosed with inflammatory bowel disease (ulcerative colitis, n = 2; Crohn’s disease, n = 1). Retrospectively, all 3 were symptomatic at the original survey. This changed the pair concordance in monozygotic twins from 6.3% to 18.8% in ulcerative colitis and from 44.4% to 50.0% in Crohn’s disease. A high degree of concordance regarding age at diagnosis, disease location at diagnosis and during the course, and disease behavior was found in concordant monozygotic twin pairs with Crohn’s disease. Seven of 9 pairs were identical in 3 or more of these disease characteristics compared with an expected number of 1.5 ( P = 0.000076). Conclusions: This study confirms that the genetic influence is stronger in Crohn’s disease than in ulcerative colitis. A remarkable phenotype similarity within concordant pairs with Crohn’s disease was found using the Vienna classification.

Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of Danish nationwide twin population

Objective: To determine the relative importance of environmental and genetic effects in the development of rheumatoid arthritis.Design: Historical cohort study with record linkage between a twin registry and the Danish...

Is the genetic liability in multifactorial disorders higher in concordant than discordant monozygotic twin pairs? A population-based family twin study of migraine without aura.

Migraine without aura (MO) is a multifactorial disorder. Expression of a disorder with multifactorial inheritance depends on the genetic liability and on environmental factors. A high liability is reflected by a high frequency of affected relatives. We have previously shown that monozygotic (MZ) twin pairs have a significant higher concordance of MO than dizygotic twin pairs. The incomplete concordance among MZ twin pairs may be due to a lower genetic liability among discordant than concordant MZ twin pairs. The present study analysed the genetic liability in MZ twin pairs concordant and discordant for MO by the population-relative risk of MO among parents and siblings. The twin pairs were from the population-based Danish Twin Register. First-degree relatives of 29 concordant and 34 discordant MZ twin pairs were blindly telephone interviewed by a physician. The participation rate of the eligible first-degree relatives was 96%. The population-relative risk of MO among parents and siblings was 2.73 (2.39-3.06) in concordant and 2.37 (2.03-2.71) in discordant MZ twin pairs. The relative risk of MO was significantly higher in female first-degree relatives of concordant than of discordant MZ male and female twin pairs. An opposite effect was observed in male first-degree relatives, although this was not significant for male first-degree relatives of female MZ twin pairs. The present study found no statistically significant difference in genetic liability to MO among concordant and discordant MZ twin pairs. However, a difference in genetic liability among MZ and DZ twin pairs is anticipated to be small. Thus, it may be possible to show the effect in a larger study population or by investigating a more frequent trait than MO.

Familial Temporal Lobe Epilepsy in Twins

A new syndrome of familial temporal lobe epilepsy is described in 38 subjects from 13 unrelated families and was first identified in 5 concordant monozygotic twin pairs at the Australian National Health and Medical Research Council Twin Registry, University of Melbourne, Parkville, Australia.

Familial temporal lobe epilepsy: a common disorder identified in twins.

We describe a new syndrome of familial temporal lobe epilepsy in 38 individuals from 13 unrelated white families. The disorder was first identified in 5 concordant monozygotic twin pairs as part of a large-scale twin study of epilepsy. When idiopathic partial epilepsy syndromes were excluded, the 5 pairs accounted for 23% of monozygotic pairs with partial epilepsies, and 38% of monozygotic pairs with partial epilepsy and no known etiology. Seizure onset for twin and nontwin subjects usually occurred during adolescence or early adult life. Seizure types were simple partial seizures with psychic or autonomic symptoms, infrequent complex partial seizures, and rare secondarily generalized seizures. Electroencephalograms revealed sparse focal temporal interictal epileptiform discharges in 22% of subjects. Magnetic resonance images appeared normal. Nine affected family members (24%) had not been diagnosed prior to the study. Pedigree analysis suggested autosomal dominant inheritance with age-dependent penetrance. The estimated segregation ratio was 0.3, indicating an overall penetrance of 60% assuming autosomal dominant inheritance. The mild and often subtle nature of the symptoms in some family members may account for lack of prior recognition of this common familial partial epilepsy. This disorder has similarities to the El mouse, a genetic model of temporal lobe epilepsy with a major gene on mouse chromosome 9, which is homologous with a region on human chromosome 3.

Discordance and concordance of dementia of the Alzheimer type (DAT) in monozygotic twins indicate heritable and sporadic forms of Alzheimer's disease

Monozygotic (MZ) twin pairs concordant for dementia of the Alzheimer type (DAT) or for proven Alzheimer's disease (AD) have a significantly higher frequency of a positive family history (DAT or AD in at least one first-degree relative, p less than 0.002) than do discordant MZ twin pairs, consistent with a lesser predicted distribution of proportions of surviving first-degree relatives without DAT (or AD) (p less than 0.001). The results suggest that concordant MZ twin pairs with DAT (or AD) have a heritable form of disease. AD in discordant twins may result from environmental influences or from a somatic chromosomal change following zygotic division.

Age at onset in schizophrenia. A familial perspective.

We examined the impact of familial factors on age at onset in schizophrenia. Results from a literature review and from new analyses of two family studies and one twin study of schizophrenia support the following hypotheses: (1) no strong or consistent relationship exists between age at onset in schizophrenia and recurrence risk for schizophrenia in relatives; (2) age at onset in schizophrenia is not strongly related to the recurrence risk for other psychiatric disorders in relatives; and (3) in systematically ascertained pairs of affected siblings, the age at onset of schizophrenia is modestly correlated, whereas the correlation in age at onset in concordant monozygotic twin pairs is much higher. These results suggest that (1) from a familial perspective, early- and late-onset adult schizophrenia appear to be the same disorder, and (2) given that an individual will develop schizophrenia, familial factors, which may be genetic, influence the age at onset of the condition.

Natural History of Psoriasis in 61 Twin Pairs

The history of psoriasis in 95 twin individuals was compared with that of a matched control group of singleton (nontwin) psoriatics. The findings indicate that twin members with psoriasis do not differ from psoriatic singletons in the general population, with respect to clinical manifestations of the disease. Psoriasis in concordant monozygotic twin pairs tended to be similar, with respect to age of onset, distribution pattern, severity, and course. This pattern was not found in concordant dizygotic twin pairs. The striking difference in rate of concordance for psoriasis between monozygotic and dizygotic twin pairs indicates that there is a heritable contribution to the etiology of psoriasis. The fact that not all monozygotic twin pairs are concordant suggests that environmental factors are also important and supports a theory of a multifactorial mode of inheritance for psoriasis.