Concordant Monozygotic Pairs Research Articles

Surgically treated degenerative disk disease in twins.

Previous studies have suggested that genetic factors are important in the development of degenerative disk disease (DDD). However, the concordance rates for the phenotypes requiring surgery are unknown. The purpose of this study was to determine the concordance rates for DDD requiring surgery by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. Patients, aged between 18 and 85years, operated for DDD between 1996 and 2022 were identified in the national Swedish spine register (Swespine) and matched with the Swedish twin registry (STR) to identify MZ and DZ twins. Pairwise and probandwise concordance rates were calculated. We identified 11,207 patients, 53% women, operated for DDD. By matching the Swespine patients with the STR, we identified 121 twin pairs (37 MZ and 84 DZ) where one or both twins were surgically treated for DDD. The total twin incidence for operated DDD was 1.1%. For DDD requiring surgery, we found no concordant MZ pair and no concordant DZ pair where both twins were operated for DDD. When we evaluated pairs where at least one twin was operated for DDD, we found two concordant MZ pairs (the co-twins were operated for spinal stenosis) and two concordant DZ pairs (one co-twin operated for spinal stenosis and one (co-twin operated for disk herniation). Our findings suggest that genetic factors are probably not a major etiologic component in most cases of DDD requiring surgery. The findings of this study can be used for counseling patients about the risk for requiring DDD surgery.

Whole-Exome Sequencing in Multiplex Families to Identify Novel AYA Classical Hodgkin Lymphoma Predisposition Genes

Background:Hodgkin Lymphoma (HL) is a B-cell malignancy that mainly affects young adults in economically developed countries. Classical HL (cHL) is the most common type, comprising >95% of cases. We demonstrated strong heritability of cHL in adolescents and young adults (AYA) with a high risk to the unaffected co-twins of affected monozygotic (MZ) twins. We and others identified common risk variants by GWAS, and sequencing of familial and sporadic HL patients previously identified rare pathogenic germline variants in genes with varying functions. Few have replicated in other families. A greater understanding of the genes involved in cHL predisposition is needed. We performed germline whole-exome sequencing (WES) for 48 individuals in 14 multiplex families with AYA cHL patients to identify novel cHL predisposition genes.Methods:Index cases from multiplex families were ascertained from the USC twin registries (International Twin Registry or California Twin Program, 7 index cases, 2 additional cases, and 7 unaffected relatives) or from the USC Cancer Surveillance Program (7 index cases, 4 additional cases, and 21 unaffected relatives). Among the twin pairs, 5 were concordant MZ pairs, one was a concordant dizygotic pair and one was an MZ discordant pair with a second case occurring in the daughter of the unaffected MZ co-twin. The other 7 families included 4 with two affected siblings, one with a child/father pair, and two with child/uncle pairs; the latter 3 families had specimens available for the index child case only. All index cases were diagnosed under 50 years old, with the median age 27.DNA samples were extracted from blood or saliva of 48 individuals in 14 multiplex families, with specimens from 20 of 28 reported cases. Germline WES was performed using the Nextera® Rapid Capture Exome kit, with data pre-processing performed based on Genome Analysis Toolkit best practices guidelines, and additional filtering applied using BCFtools. Variants were annotated using ANNOVAR. We filtered out variants with an allele frequency >0.001 in population databases (gnomAD or TOPMed), and variants documented as benign/likely benign in ClinVar. We retained splicing/ncRNA variants and exonic variants with loss-of-function/missense/unknown functional consequences, and with a CADD score >10. We further limited variants to those in 1,073 candidate predisposition genes, including cancer/immunodeficiency/hematological-related genes in the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) and genes previously identified in sequencing studies or GWAS for cHL. Variants in candidate genes were visually inspected in the Integrative Genomics Viewer and were analyzed for their potential pathogenicity through the PeCanPIE MedalCeremony pipeline. Variants predicted to be tolerated by PeCanPIE were removed. Variants found only in HL patients and not in their sibling controls were considered to be potentially causal.Results:In 45 subjects that passed sequencing QC (3 controls were removed due to low mean coverage) and following variant filtering, there were 33 variants in 33 genes found only in cHL patients but not in their sibling controls, among 9 of 14 families. None of the variants appeared in more than one family.One variant in PGK1 was previously reported as pathogenic/likely pathogenic in ClinVar in patients with phosphoglycerate kinase 1 deficiency associated with hemolytic anemia. Nine variants were reported in ClinVar as variants of uncertain significance, of which 3 were previously reported in patients with immunodeficiency disorders (in genes IL2RA, MALT1, and PRKDC) and 2 were reported in patients with dyskeratosis congenita (TERT) and other anemia-associated disorders (EPB42). Of 22 variants not reported in ClinVar, one was a missense variant in NPAT, a gene previously associated with familial lymphoma; 4 were in genes associated with immune disorders (PLCG2, LIG1, C1QB, and NOD2) and 3 were in genes associated with anemia (SPTB, ALDOA, and GATA1). To our knowledge, none of these genes other than NPAT have previously been implicated in predisposition to HL.Conclusions:WES in 20 AYA cHL patients among multiplex families identified putative novel predisposition genes for HL, including genes implicated in anemia and immune function. Assessment of these genes in sequencing studies of independent HL families is required to understand their role in HL predisposition. DisclosuresWadé: Flatiron Health: Current Employment; Roche: Current equity holder in publicly-traded company.

Genetics of febrile seizure subtypes and syndromes: A twin study

Febrile seizures (FS) are the most common seizure syndrome. A strong genetic component has been well established through family and twin studies; however, such studies have not examined the genetics of different FS types (simple, complex, febrile status epilepticus) and sub-syndromes (true FS, febrile seizures plus (FS+), 'FS with later epilepsy'). Here we used a community-based twin sample to analyze genetic factors within different FS subtypes and FS syndromes. Twin pairs were ascertained from the twin database of the Epilepsy Research Centre. A retrospective chart review was conducted and follow-up attempted for all subjects. Casewise concordance values were calculated for the different subgroups and intra-pair variation was analyzed. One hundred and seventy-nine twin pairs with FS were identified. Overall casewise concordance for FS in monozygotic (MZ) twins (0.62) was greater than in dizygotic (DZ) twins (0.16, p<0.0001). A greater concordance amongst MZ pairs than DZ twin pairs was also observed for all FS subtypes and FS sub-syndromes, particularly in twins with FS+. Within concordant MZ pairs, we did not observe the co-occurrence of FS and FS+. These results suggest a strong genetic contribution to different FS subtypes and sub-syndromes. They also support the existence of distinct genetic factors for different FS subtypes and sub-syndromes, especially FS+. This information is important for the strategic planning of next generation sequencing studies of febrile seizures.

Epicardial Fat, Cardiac Dimensions, and Low-Grade Inflammation in Young Adult Monozygotic Twins Discordant for Obesity

Epicardial fat with its close proximity to coronary arteries has been suggested to be a significant predictor of cardiovascular disease. We studied the relations among acquired obesity, low-grade inflammation, and genetic factors in the accumulation of epicardial fat. A rare sample (n = 15) of healthy monozygotic (MZ) twin pairs discordant for obesity (intrapair difference in body mass index ≥3 kg/m(2)) and 9 concordant MZ pairs 23 to 33 years old were examined for cardiac structure, function, epicardial fat thickness (echocardiography), abdominal subcutaneous tissue, and visceral adipose tissue (VAT), liver fat (magnetic resonance imaging/spectroscopy), and serum high-sensitivity C-reactive protein. In the entire sample, MZ cotwins were remarkably similar in most echocardiographic measurements including epicardial fat (intraclass correlation 0.63, p = 0.0004). However, in the discordant pairs, the obese cotwins (16.5 kg, 23% heavier) had 26% more epicardial fat (p = 0.0029) than nonobese cotwins. They also had significantly larger atrial and left ventricular dimensions. Epicardial fat correlated with VAT (r = 0.49, p = 0.02) in individual twins and when using intrapair differences of measurements within pairs (r = 0.39, p = 0.06). In multiple regression analyses including abdominal subcutaneous tissue, VAT, and liver fat, high-sensitivity C-reactive protein was the only factor that remained significantly associated with epicardial fat in individual twins and within pairs. In conclusion, subjects who share the same genes seem to have similar cardiac dimensions. However, acquired obesity increases epicardial fat independent of genetic factors. The close relation between epicardial fat and low-grade inflammation is likely to contribute to the development of cardiovascular disease in obesity.

Idiopathic mesial temporal lobe epilepsy: a syndrome with complex inheritance?

In a recent article, Striano et al. [1] stated that familial mesial temporal lobe epilepsy was consistent with an autosomal dominant inheritance with incomplete penetrance. In fact, this pattern of inheritance was already proposed when the syndrome was recognized by Berkovic et al. [2]. Subsequently, others researchers extended the clinical spectrum of the disorder, but they still supported the same mode of genetic transmission [3, 4]. However, some observations could point against this general agreement. First, no very large pedigrees of familial mesial temporal lobe epilepsy have been reported to date [5]. In addition, 15 out of 39 pedigrees included in three of the referred series showed that all the affected members belonged to the proband’s generation [1–3], which would be unusual for an autosomal dominant inheritance. This would explain why only isolated families with different subtypes of the disorder have, so far, been mapped [6, 7]. On the other hand, the way in which the reported patients were ascertained could have caused a selection bias and, consequently, an inappropriate conclusion about the pattern of inheritance. Cases published in the four series cited above had to have one or more affected first-degree relatives to be included in the study [1–4]. This mode of recruitment determines that the families selected will automatically contain a high proportion of affected members [8]. However, there might be in the community other families with the same disorder, but with a single individual affected. The possibility that such families would be improperly excluded leads Ottmann to consider that the mode of inheritance of this syndrome is still uncertain [8]. Patients with sporadic presentation, but an otherwise similar phenotype to those with familial mesial temporal lobe epilepsy, have been described in the literature in several hospital series [9–12]. Compared to familial patients, these sporadic cases had identical seizure types, the same lack of acquired risk factors for epilepsy and a history of normal psychomotor development. Furthermore, the sporadic type was more prevalent than the familial one in these series. Although some of the previous observations could be explained by reduced penetrance of an autosomal dominant disorder, others would undoubtedly be more concordant with a disorder with complex inheritance. Until genetic studies support a different approach, it seems logical to include both sporadic and familial cases consistent with this syndrome under the name of ‘‘idiopathic mesial temporal lobe epilepsy’’ (IMTLE). As Berkovic et al. stated, twin studies allow an easy recognition of a genetic disorder even if the mode of inheritance is complex [2]. In fact, they initially identified familial mesial temporal lobe epilepsy in this manner. Later on, families that had a similar syndrome, collected from the private and hospital practice of one of the investigators, were added to this Australian series. As they admitted in their article, the twin families, taken from community-based registers, could be more representative of the general population than their nontwin families. However, after a segregation analysis, which included only their nontwin families, the authors concluded that the disorder was suggestive of an autosomal dominant inheritance with reduced penetrance. In their study, among five families of concordant monozygotic pairs, only one pedigree showed some other affected relatives, which led them to suggest that this genetic disorder could also be a frequent cause of apparently sporadic cases. Therefore, it could be reasonable to support the inclusion of all cases of the J. Gomez-Alonso (&) D. Munoz-Garcia M. Aguado Servicio de Neurologia, Hospital Xeral-Cies, Pizarro 22, 36204 Vigo, Spain e-mail: juan.gomez.alonso@sergas.es

Environmental Factors in Obsessive-Compulsive Behavior: Evidence from Discordant and Concordant Monozygotic Twins

To investigate environmental factors that protect against or exacerbate obsessive-compulsive (OC) symptoms, we selected 25 monozygotic (MZ) twin pairs discordant, 17 MZ twin pairs concordant high and 34 MZ pairs concordant low on OC symptoms from a large longitudinal Dutch sample of adult twin pairs and their family members, applying stringent criteria for OC symptomatology. Data were collected on psychopathology, family structure, health, lifestyle, birth complications and life events. Unique environmental factors were studied using within-discordant MZ pair comparisons, whereas between-concordant MZ pair comparisons were used to study environmental factors that are shared by the twins of an MZ pair. The high-scoring MZ twins of the discordant group reported more life events (especially sexual abuse) than their low-scoring twin-siblings. The between-pair comparisons showed lower birth weight in the discordant MZ pairs than in the concordant MZ pairs. Further, the concordant high MZ pairs as well as their spouses had a lower educational level than the two other groups. On scale scores of anxious-depression, neuroticism, and somatic complaints, concordant high MZ pairs showed highest scores, and the discordant MZ pairs scored intermediate, except for neuroticism, on which the high-scoring twins of discordant MZ pairs were equal to the concordant high pairs. Discordance on psychological scale scores between the concordant MZ pairs was evident from 1991 onward, and within the discordant MZ pairs from 1997 onward, confirming previous reports of an association of early-onset OC symptoms with higher genetic load. Parent scores of OC symptoms and anxious-depression suggested intermediate genetic load in the discordant MZ group. In conclusion, this study reports on both unique and shared environmental factors associated with OC symptomatology. Whether these factors operate in addition to or in interaction with genetic disposition is to be elucidated in future studies.

Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease

The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD.

Neurological soft signs and dermatoglyphic anomalies in twins with schizophrenia

Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a–b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discordant compared to concordant monozygotic pairs. There was no significant difference in NSS and TABRC scores between subjects with schizophrenia and their co-twins without the illness. However, monozygotic discordant twins with schizophrenia had higher ABRCs on their right hands compared to their co-twins without the illness. These findings suggest that an unidentified environmental event acting between weeks 6 and 15 of gestation affects the development of monozygotic twins who go on to develop schizophrenia but does not have a corresponding effect on their co-twins who do not develop the illness. The effect of such an event on dermatoglyphic profiles appears lateralised to the right hand in affected twins.

A note on cluster headache in a population-based twin register.

Evidence of a familial risk factor in cluster headache is accumulating and studies of twin concordance may resolve family resemblance into genetic and environmental influences. The past literature on cluster headache in twins comprises a few case reports of concordant monozygotic pairs. Swedish twin pairs with a diagnosis of cluster headache were selected through a cross-match of national registers of twin births and hospitalizations. Seventeen discordant twin pairs were found, in which it was possible to verify cluster headache status in 11 complete pairs (two monozygotic, four dizygotic, and five unlike-sexed pairs). In both members of a female monozygotic pair, migraine without aura developed after birth of the first child and remitted by menopause, whereas post-menopausal development of chronic cluster headache occurred in only one of them. The importance of individual specific factors for cluster headache was demonstrated. However, to explain familial aggregation a larger sample of affected twin pairs is necessary.

First-episode psychosis: A comparative study of patients with short versus long duration of untreated illness

Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a–b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discordant compared to concordant monozygotic pairs. There was no significant difference in NSS and TABRC scores between subjects with schizophrenia and their co-twins without the illness. However, monozygotic discordant twins with schizophrenia had higher ABRCs on their right hands compared to their co-twins without the illness. These findings suggest that an unidentified environmental event acting between weeks 6 and 15 of gestation affects the development of monozygotic twins who go on to develop schizophrenia but does not have a corresponding effect on their co-twins who do not develop the illness. The effect of such an event on dermatoglyphic profiles appears lateralised to the right hand in affected twins.

Alzheimer's disease in Finnish twins

Summary Background The genetics of Alzheimer's disease (AD) are obscure. Although most cases are sporadic half the patients with sporadic AD have a positive family history. The mode of genetic transmission and the role of environmental factors are unknown. The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AD in a twin cohort. Methods The Finnish Twin Cohort consists of all Finnish same-sexed twin pairs born before 1958 with both co-twins alive in 1975. The total number of twin pairs is 13 888, of whom 4307 are monozygotic (MZ) and 9581 are dizygotic (DZ). These data were linked with the Hospital Discharge Register from 1972 to 1991 to identify twins who had dementia or related disease as a discharge diagnosis. The linkage of the registries yielded a total of 285 twin individuals. The medical records of these twins and their co-twins were reviewed to confirm and classify dementia (AD, vascular dementia, mixed dementia, and other dementia). The incidence, concordance, and age at onset of AD were examined. Findings The incidence of AD was significantly higher in MZ than in DZ twin individuals, with an adjusted MZ/DZ incidence ratio of 1·8 (95% confidence intervals 1·2 to 2·7). In contrast, the incidence of vascular or mixed dementia did not differ between MZ and DZ individuals (MZ/DZ ratio 0·6 [0·3 to 1·2]) for vascular and 1·0 [0·5 to 2·1] for mixed dementia). The pairwise concordance for AD was 18·6% in MZ pairs and 4·7% in DZ pairs and the corresponding probandwise concordance rates were 31·3% and 9·3%. The pairwise concordance for vascular dementia was 18·2% in MZ pairs and 6·7% in DZ pairs with corresponding probandwise rates of 30·8% and 12·5%. The onset age of AD in concordant MZ pairs was identical in two pairs and diverged by up to 15 years. Interpretation The higher incidence of AD in MZ individuals than in DZ individuals may provide a clue to the aetiology of AD. The higher concordance rate of MZ pairs confirms the contribution of the major genetic component while indicating the need to identify environmental triggers.

Prenatal development of monozygotic twins and concordance for schizophrenia.

While twin concordances for schizophrenia have been used to estimate heritability and to develop genetic models, concordances in subtypes of monozygotic (MZ) twins can also be used to investigate the influence of prenatal development in the etiology of mental illness. We used within-pair variability and mirroring of fingerprints to estimate retrospectively the placentation status of concordant and discordant MZ twins. The results indicate that concordant MZ pairs were more likely to have been monochorionic (MC) and to have shared a single placenta, whereas discordant MZ pairs appear more likely to have been dichorionic (DC) with separate placentas. Pairwise concordances for MZ twins without MC markers averaged 10.7 percent. In contrast, concordances for MZ twins with one or more MC markers averaged 60 percent. This suggests that simple MZ concordance rates may overestimate schizophrenia heritability and that prenatal development may also be important in the etiology of schizophrenia. Because MC (but not DC) twins usually share fetal blood circulation and hence are likely to share infections, these results are consistent with the hypothesis that fetal infections may be a significant etiological factor in schizophrenia.

Summary

Febrile seizures (FS) are the most common seizure syndrome. A strong genetic component has been well established through family and twin studies; however, such studies have not examined the genetics of different FS types (simple, complex, febrile status epilepticus) and sub-syndromes (true FS, febrile seizures plus (FS+), ‘FS with later epilepsy’). Here we used a community-based twin sample to analyze genetic factors within different FS subtypes and FS syndromes.Twin pairs were ascertained from the twin database of the Epilepsy Research Centre. A retrospective chart review was conducted and follow-up attempted for all subjects. Casewise concordance values were calculated for the different subgroups and intra-pair variation was analyzed.One hundred and seventy-nine twin pairs with FS were identified. Overall casewise concordance for FS in monozygotic (MZ) twins (0.62) was greater than in dizygotic (DZ) twins (0.16, p < 0.0001). A greater concordance amongst MZ pairs than DZ twin pairs was also observed for all FS subtypes and FS sub-syndromes, particularly in twins with FS+. Within concordant MZ pairs, we did not observe the co-occurrence of FS and FS+.These results suggest a strong genetic contribution to different FS subtypes and sub-syndromes. They also support the existence of distinct genetic factors for different FS subtypes and sub-syndromes, especially FS+. This information is important for the strategic planning of next generation sequencing studies of febrile seizures.

A Genetic Study of Male Sexual Orientation

Homosexual male probands with monozygotic cotwins, dizygotic cotwins, or adoptive brothers were recruited using homophile publications. Sexual orientation of relatives was assessed either by asking relatives directly, or when this was impossible, asking the probands. Of the relatives whose sexual orientation could be rated, 52% (29/56) of monozygotic cotwins, 22% (12/54) of dizygotic cotwins, and 11% (6/57) of adoptive brothers were homosexual. Heritabilities were substantial under a wide range of assumptions about the population base rate of homosexuality and ascertainment bias. However, the rate of homosexuality among nontwin biological siblings, as reported by probands, 9.2% (13/142), was significantly lower than would be predicted by a simple genetic hypothesis and other published reports. A proband's self-reported history of childhood gender non-conformity did not predict homosexuality in relatives in any of the three subsamples. Thus, childhood gender nonconformity does not appear to be an indicator of genetic loading for homosexuality. Cotwins from concordant monozygotic pairs were very similar for childhood gender nonconformity.

Genetic factors in epileptic seizures: evidence from a large twin population

The Finnish Twin Cohort study (27,776 individuals; all twins of the same sex born before 1958 and alive in 1967) detected 316 cases of epileptic seizures occurring in 310 twin pairs: 89 monozygotic pairs and 221 dizygotic pairs, including three concordant monozygotic pairs and three concordant dizygotic pairs. The ratio of the observed to expected number of concordant pairs for epileptic seizures was 5.48 (90% CL 1.5-14.2) in monozygotic and 2.12 (90% CL 0.6-5.5) in dizygotic pairs. The results suggest that 8% to 27% of the incidence of epileptic seizures is related to genetic variability. The study of environmental differences in discordant monozygotic pairs should provide insights into the etiology of this group of disorders.

Psoriasis in an Unselected Series of Twins

The relative importance of genetic factors in the origin, age at onset, clinical type, course, and severity of psoriasis was evaluated on the basis of an unbiased sample of twins, ie, the Danish Twin Register, which covers the total population of twins born in Denmark. All verified and probable cases of psoriasis in twins, born 1891 through 1920, were ascertained. Results are presented of an examination of all members of index pairs in which both partners were alive on a certain date. Fourteen monozygotic and 22 dizygotic, like-sexed pairs were found to include at least one partner with unquestionable psoriasis. Zygosity determination was mainly based on extensive serological examinations. The analyses show that the manifestation of psoriasis depends almost exclusively on the presence of the specific genotype. The age at onset, clinical type, course, and severity are also mainly determined by the genetic constitution. Association with certain HLA antigens of the B series has been confirmed, but the fact that many of the twins (including several of the concordant monozygotic pairs) possess neither of these antigens shows the corresponding genes to be important, but not decisive, elements in the predisposition. We conclude that psoriasis is a genetically determined disorder that may, to a limited extent, be modified by environmental influences.