Genetic and environmental contributions to population group differences on the Raven's Progressive Matrices estimated from twins reared together and apart

We carried out two studies to test the hypothesis that genetic and environmental influences explain population group differences in general mental ability just as they do individual differences within a group. We estimated the heritability and environmentality of scores on the diagrammatic puzzles of the Raven's Coloured and/or Standard Progressive Matrices (CPM/SPM) from two independent twin samples and correlated these estimates with group differences on the same items. In Study 1, 199 pairs of 5- to 7-year-old monozygotic (MZ) and dizygotic (DZ) twins reared together provided estimates of heritability and environmentality for 36 puzzles from the CPM. These estimates correlated with the differences between the twins and 94 Serbian Roma (both rs=0.32; Ns=36; ps<0.05). In Study 2, 152 pairs of adult MZ and DZ twins reared apart provided estimates of heritability and environmentality for 58 puzzles from the SPM. These estimates correlated with the differences among 11 diverse samples including (i) the reared-apart twins, (ii) another sample of Serbian Roma, and (iii) East Asian, White, South Asian, Coloured and Black high school and university students in South Africa. In 55 comparisons, group differences were more pronounced on the more heritable and on the more environmental items (mean rs=0.40 and 0.47, respectively; Ns=58; ps<0.05). After controlling for measurement reliability and variance in item pass rates, the heritabilities still correlated with the group differences, although the environmentalities did not. Puzzles found relatively difficult (or easy) by the twins were those found relatively difficult (or easy) by the others (mean r=0.87). These results suggest that population group differences are part of the normal variation expected within a universal human cognition.     

The personalities of twins: just ordinary folks.

Twin studies have demonstrated that personality traits show moderate genetic influence. The conclusions drawn from twin studies rely on the assumptions that twins are representative of the population at large and that monozygotic and dizygotic twins are comparable in every way that might have bearing on the traits being studied. To evaluate these assumptions, we used Multidimensional Personality Questionnaire (MPQ) data from three samples drawn from the Minnesota Twin Registry (totaling 12,971 respondents) to examine the effect sizes associated with mean differences on the 11 MPQ scales and 3 higher-order MPQ factors for singletons versus twins and MZ twins versus DZ twins. The singletons in the samples were family members of the participating twins. We also used ratios of scale variances to examine the significance of variance differences. The only mean or variance difference replicated across all three samples was greater Social Closeness (about.1 standard deviation) for twins than for singletons. This difference was obtained for both males and females. It would appear that, with respect to personality, twins are not systematically different from other people. Our results also highlight the importance of replication in psychological research because each of our large samples showed differences not replicated in other samples.     

The mechanism of emergenesis

Since each individual produced by the sexual process contains a unique set of genes, very exceptional combinations of genes are unlikely to appear twice even within the same family. E. O. Wilson (1978)The intraclass correlations of monozygotic twins who were separated in infancy and reared apart (MZA twins) provide estimates of trait heritability, and the Minnesota Study of Twins Reared Apart [MISTRA: Bouchard et al. (1990), The sources of human psychological differences: the Minnesota study of twins reared apart, Science 250, 223-228] has demonstrated that MZA pairs are as similar in most respects as MZ pairs reared together. Some polygenic traits--e.g. stature, IQ, harm avoidance, negative emotionality, interest in sports--are polygenic-additive, so pairs of relatives resemble one another on the given trait in proportion to their genetic similarity. But the existence and the intensity of other important psychological traits seem to be emergent properties of gene configurations (or configurations of independent and partially genetic traits) that interact multiplicatively rather than additively. Monozygotic (MZ) twins may be strongly correlated on such emergenic traits, while the similarity of dizygotic (DZ) twins, sibs or parent-offspring pairs may be much less than half that of MZ pairs. Some emergenic traits, although strongly genetic, do not appear to run in families. MISTRA has provided at least two examples of traits for which MZA twins are strongly correlated, and DZA pairs correlate near zero, while DZ pairs reared together (DZTs) are about half as similar as MZTs. These findings suggest that even more traits may be emergenic than those already identified. Studies of adoptees reared together (who are perhaps more common than twins reared apart) may help to identify traits that are emergenic, but that also are influenced by a common rearing environment.     

Genetic determination of the human EEG

Summary In this article, we have discussed recent progress in quantifying the genetically determined component of the resting EEG. This progress has been made possible in particular by the application of advanced information processing techniques such as supervised learning, and the development of a problem-oriented similarity concept. Our work aimed at modeling previous findings regarding the distinct individuality of human brain-wave patterns, the high similarity between the EEGs of monozygotic twins, and the average within-pair similarity of dizygotic twins. Thus, we had three objectives: First, we wanted to improve the quantification of EEG characteristics with respect to reproducibility and specificity by means of adaptive procedures and repeated measurements. Second, we wanted to compare the typical within-subject EEG similarity with the typical within-pair EEG similarity of monozygotic and dizygotic twins brought up together. Finally, we were interested in the degree to which environmental factors affect the characteristics of human brain-wave patterns. Our investigations were based on the empirical data derived from five different populations: (1) 81 healthy subjects, (2) 24 pairs of monozygotic twins brought up together, (3) 25 pairs of dizygotic twins brought up together, (4) 28 pairs of monozygotic twins reared apart, and (5) 21 pairs of dizygotic twins reared apart. Following our similarity conception, repeated measurements on the set of 81 individuals were used as design samples, and new registrations from the same individuals taken 14 days later were referred to as test samples in order to develop the appropriate method and to determine all required calibration parameters. This specific approach allowed us to construct EEG spectral patterns which, with a specificity and reproductibility of>90% each, largely met the requirements of genetic EEG studies. Hence, we were able systematically to investigate the within-pair EEG similarity of our twin samples. Our results provided ample evidence that the individual characteristics of the resting EEG are primarily determined by genetic factors: (1) There exists an almost perfect one-to-one mapping between each individual and his EEG; (2) monozygotic twins proved, with respect to their resting EEGs, to be only slightly less like one another (if there is any difference at all) than each person is to himself over time; (3) the average within-pair EEG similarity estimated from a sufficiently representative sample of dizygotic twins is significantly above the inter-individual EEG similarity between unrelated persons (this finding holds true for both samples of dizygotic twins brought up together and reared apart, and there is also no statistically significant difference in the resting EEG between these two samples) and, (4) the EEGs of monozygotic twins reared apart are obviously as similar to each other as are the EEGs of the same person over time, and there is no statistically significant difference in the resting EEG between the two populations of monozygotic twins brought up together and monozygotic zygotic twins reared apart.     

The behaviour of twin rhesus monkeys and comparisons with the behaviour of single infants

Twin rhesus monkeys, born in a laboratory cage, were reared alone with their mother for a year. Observations were made of mother-infant interactions. Differences between the infants which concerned the amount of time spent off the mother seem to have been due to differences in the behaviour of the mother towards the two twins, whereas differences between measures of behaviour while off the mother seem to have been due to differences between the twins. The twins also differed in activity and in responses to mildly frightening or strange situations. The behaviour of the twins was compared with that of two single infants reared under the same cage conditions and also alone with their mothers. Some differences were found between the twins and the singles in mother-infant interaction, and there were also some differences in activity and in responses to mildly frightening or strange situations.     

Netherlands Twin Register: a focus on longitudinal research.

In 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a questionnaire at registration and afterwards when the children are 2, 3, 5, 7, 10 and 12 years of age. Teachers are asked to rate the behavior of the children at ages 7, 10 and 12 years. Adolescent and young-adult twins were recruited through City Councils in the early 1990s. These twins, their parents and siblings participate in longitudinal survey studies that include items about health, fertility, lifestyle, addiction, personality and psychopathology, religion, socioeconomic status, and educational attainment. The total number of twins and multiples registered with the NTR is currently over 60,000. Subgroups of twins and siblings take part in studies of cognitive development, brain function and neuropsychological indices of attention processes, and molecular genetic studies of classical and behavioral cardiovascular risk factors. DNA samples are currently collected in selected twin families for two large linkage studies, which aim to find QTLs for anxious depression and for nicotine addiction. Sisters who are mothers of DZ twins contribute DNA samples for a linkage study of DZ twinning. Large cohorts of phenotyped family members from the general population are very valuable for genetic epidemiological studies and permit selection of informative families for gene finding studies.     

Atopic disease and immunoglobulin E in twins reared apart and together.

Both genetic and environmental influences have been implicated in the etiology of atopic disease and in the determination of serum IgE levels. To quantify the relative contribution of these influences, we studied the prevalence of asthma and seasonal rhinitis, skin-test response, total serum IgE levels, and specific IgE, as measured by RAST, in a sample of MZ and DZ twins reared apart or together. Concordance rates for asthma, rhinitis, positive skin tests, and RAST were calculated. MZ twins, whether reared apart or together, showed a greater concordance than dizygotic twins reared apart or together. Maximum-likelihood tests of genetic and environmental components of the variation of total IgE levels revealed a substantial genetic component and a negligible contribution from common familial environmental effects.     

圈养大熊猫母兽成功哺育双胞胎成活初探

圈养大熊猫产下双胞胎后,母兽一般难以同时哺育二仔。2003年,圈养大熊猫母兽“梅梅”同时哺育双胞胎成活,本文对该首例哺育双胞胎成活的原因进行了初步分析,认为满足母兽的营养需求、适宜的育幼环境及人工护理,特别是“梅梅”的母性好、有丰富的育幼经验、食欲强、泌乳充足等在同时哺育双胞胎成活中起着重要作用,同时对“梅梅”哺育的双胞胎与其哺育的另两只单胎幼仔的体重增长情况进行了比较,为圈养大熊猫成功哺育双胞胎,增加幼仔成活率,提供了有关借鉴信息和资料。     

A case of true hermaphroditism reveals an unusual mechanism of twinning

Traditionally twins are classified as dizygous or fraternal and monozygous or identical (Hall Twinning, 362, 2003 and 735-743). We report a rare case of 46,XX/46,XY twins: Twin A presented with ambiguous genitalia and Twin B was a phenotypically normal male. These twins demonstrate a third, previously unreported mechanism for twinning. The twins underwent initial investigation with 17-hydroxyprogesterone and testosterone levels, pelvic ultrasound and diagnostic laparoscopy. Cytogenetic analysis was performed on peripheral blood cells and skin fibroblasts. Histological examination and Fluorescence in situ hybridization studies on touch imprints were performed on gonadal biopsies. DNA analysis using more than 6,000 DNA markers was performed on skin fibroblast samples from the twins and on peripheral blood samples from both parents. Twin A was determined to be a true hermaphrodite and Twin B an apparently normal male. Both twins had a 46,XX/46,XY chromosome complement in peripheral lymphocytes, skin fibroblasts, and gonadal biopsies. The proportion of XX to XY cells varied between the twins and the tissues evaluated. Most significantly the twins shared 100% of maternal alleles and approximately 50% of paternal alleles in DNA analysis of skin fibroblasts. The twins are chimeric and share a single genetic contribution from their mother but have two genetic contributions from their father thus supporting the existence of a third, previously unreported type of twinning.     

A gerontological cohort study of aged twins: the Osaka University Aged Twin Registry.

We describe subject recruitment and research results from the Osaka University Aged Twin Registry (OUATR). The research focus of OUATR is the genetic and environmental contributions to physical-cognitive-mental aging which we examined in Japanese twins in later adulthood. Within this large-scale registry (12,000 pairs) of oriental twins born between 1900 and 1935, approximately 10% of participants are MZ twins reared apart from early childhood. Two hundred and fifty pairs have had comprehensive medical examinations, including various blood chemical panels, lymphocyte subtests, WAIS (Wechsler Adult Intelligence Scale), and urine analysis. The future foci of this study are primarily on longevity, decline of cognitive functions with aging, bio-physiological functions, lifestyle and behavior genetics, and psycho-spiritual functions.     

La presencia de algún trastorno psiquiátrico podría alterar el reloj epigenético en gemelos monocigóticos

BackgroundThe acceleration of the epigenetic clock has been associated with a reduction in life expectancy. Individuals diagnosed with a psychiatric disorder have a reduction in life expectancy, and some studies have correlated it with accelerated aging.ObjectiveThe present study aims to explore whether the presence of any psychiatric disorder could accelerate the epigenetic clock in monozygotic twins.MethodsA total of 15 pairs of monozygotic twins were included. Epigenetic age in peripheral blood cells was estimated by previously published algorithms, using the 450K Beadchip microarray.ResultsWe found that in twins with a diagnosis of a psychiatric disorder, the epigenetic clock could increase compared to their twin without a psychiatric disorder.Discussion and conclusionThe presence of some psychiatric disorder could accelerate the epigenetic clock in homozygous twins, but studies with larger samples are required to clarify this relationship.     

Glucose and insulin metabolism in twins: influence of zygosity and birth weight.

Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.     

Twin-Based DNA Methylation Analysis Takes the Center Stage of Studies of Human Complex Diseases

The etiology of complex diseases is characterized by the interaction between the genome and environmental conditions and the interface of epigenetics may be a central mechanism. Current technologies already allow us high-throughput profiling of epigenetic patterns at genome level. However, our understanding of the epigenetic processes remains limited. Twins are special samples in genetic studies due to their genetic similarity and rearing-environment sharing. In the past decades, twins have made a great contribution in dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable samples of twins are helping to bridge the gap between gene activity and environmental conditions through epigenetic mechanisms unlimited to DNA sequence variations. We review the recent progresses in using twins to study disease-related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Various study designs and application issues will be highlighted and discussed with aim at making uses of twins in assessing the environmental impact on epigenetic changes during the development of complex diseases.     

Genetic and environmental correlations among serum lipids and apolipoproteins in elderly twins reared together and apart.

Genetic and environmental correlations among five serum-lipid measures were examined in the Swedish Adoption/Twin Study of Aging. The sample included 302 twin pairs; 146 of these twin pairs were separated at an early age and were reared apart. The lipid measures examined include total cholesterol, HDL-cholesterol, triglycerides, and apolipoproteins A-I and B. Genetic and environmental correlations were evaluated for two different age groups, formed by dividing the sample at the median. The younger group included individuals 41.8-65.4 years of age at the midpoint of testing, although only 24 individuals were < 50 years of age. The older group included all those > 65.4 years of age, up to age 87 years of age. Substantial genetic correlations were found within each age group, although there is no evidence for a single genetic factor common to all five lipids. The comparison of twins reared together with twins reared apart allowed estimation of the effects of shared rearing environment; however, shared rearing environment only appears to be a significant mediator of the phenotypic correlation between apolipoprotein B and cholesterol in the older group. Examination of the genetic and environmental covariances suggests that the relative contributions of genetic factors are lower in the older group. Nonshared environmental factors are relatively more important mediators of phenotypic correlations among the serum lipids in individuals > 65.4 years of age than they are for the younger group. Sex differences in the mediation of these serum lipids were not as clear.     

On the twin risk in autism

Autism is considered by many to be the most strongly genetically influenced multifactorial childhood psychiatric disorder. In the absence of any known gene or genes, the main support for this is derived from family and twin studies. Two recent studies (Greenberg et al. 2001; Betancur et al. 2002) suggested that the twinning process itself is an important risk factor in the development of autism. If true, this would have major consequences for the interpretation of twin studies. Both studies compared the number of affected twin pairs among affected sib pairs to expected values in two separate samples of multiplex families and reported a substantial and significant excess of twin pairs. Using data from our epidemiological study in Western Australia, we investigated the possibility of an increased rate of autism in twins. All children born between 1980 and 1995 with autism, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) were ascertained. Of the 465 children with a diagnosis, 14 were twin births (rate 30.0/1,000) compared to 9,640 children of multiple births out of a total of 386,637 births in Western Australia between 1980 and 1995 (twin rate weighted to number of children with autism or PDD per year 26.3/1,000). These data clearly do not support twinning as a substantial risk factor in the etiology of autism. We demonstrate that the high proportion of twins found in affected-sib-pair studies can be adequately explained by the high ratio of concordance rates in monozygotic (MZ) twins versus siblings and the distribution of family size in the population studied. Our results are in agreement with those of two similar studies by Croen et al. (2002) in California and Hultman et al. (2002) in Sweden.     

Social discrimination in lambs: the role of indirect familiarization and methods of assessment

Familiarization with individuals resulting from direct exposure is the primary mechanism mediating social recognition in many vertebrates. However, discernible phenotypic similarity among close kin may provide an additional basis for recognizing previously unencountered individuals. We investigated the existence of such a mechanism of indirect familiarity among artificially reared twin lambs, Ovis aries, that were separated shortly after birth. When they were 2-3 weeks old, we tested their recognition of familiar penmates, their unfamiliar twin and twins of familiar penmates in two-choice and paired tests. Lambs responded discriminatively to familiar penmates. When allowed to choose between their twins or twins of penmates versus an unfamiliar unrelated individual, lambs did not show any preference. Nevertheless, when paired with a twin or penmate’s twin, lambs bleated less than did those paired with an unfamiliar unrelated partner, which suggests that twins and twins of penmates were recognized. Discrimination between twin and unrelated individuals could be based either on early learning of the twin's phenotypic traits (template) before separation or on a process of indirect familiarization (comparison with familiar self cues). However, indirect familiarization was clearly implicated in the discrimination of twins of penmates; that is, lambs learned the characteristic phenotypic traits of (unrelated) penmates and detected a resemblance between those familiar individuals and their twins. Overall, the two-choice and paired tests were differentially effective procedures depending on the research question being addressed, that is, relatively simple or subtle social discrimination. Copyright 2003 Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour.      

Twinning frequency of Japanese Macaques (<Emphasis Type="Italic">Macaca fuscata</Emphasis>) at Takasakiyama

In a wild-living, artificially provisioned population of Japanese macaques at Takasakiyama in southern Japan, nine sets of twins were recorded from 12,392 known deliveries over a 56-year study period. Recorded twinning frequency was 0.073%. During the first 28-year period, artificial food was given until macaques were satiated and population size increased rapidly. In the second 28-year period, provisioned food was restricted to about half of the former period’s calorific content. Seven sets of twins were born in the first period and two sets in the second. Twining frequency in the two periods was 0.137 and 0.027%, respectively. In comparing studies of other Catarrhine primate samples, we hypothesize that twinning frequency is influenced by living conditions, and we suggest that living conditions should be carefully evaluated in studies of twinning frequency.     

Representativeness of a roster of volunteer North American twins with chronic disease.

To identify large numbers of twins affected by chronic disease as potential subjects for studies of environmental and genetic chronic disease determinants, we advertised for affected twins over the period 1980-91 in newspapers across North America. Responses were received from 17 245 twin pairs in which cases of cancer or other chronic disease had occurred. To assess the representativeness of affected twins identified by advertising, we evaluated the pattern of reporting, compared the cases identified to the number of cases estimated to be prevalent among all North American twins, compared the cases to population-based singleton case series, compared the healthy co-twins to population-based samples of healthy persons, assessed the impact on ascertainment of opinions about disease causation, compared the pattern of prospective to retrospective ascertainment of disease in the originally unaffected co-twins of cases, and compared the results of the prospective ascertainment of disease in co-twins to comparable published estimates. Youth, gender, zygosity, education, and disease concordance were found to be overall determinants of ascertainment. Disease-discordant DZ twins appeared to be modestly underascertained. While somewhat better educated, both concordant and discordant pairs were judged to be reasonably representative of affected non-Hispanic white North American twin pairs of comparable status, ie of comparable age, sex, race, and zygosity. If interpreted with caution, the concordance patterns of such twins can be used to generate genetic hypotheses, but should not be the basis of definitive heritability analyses. We conclude that advertising offers a method of identifying pairs of twins that can serve as subjects for studies designed to identify disease determinants.     

Whole genome and exome sequencing of monozygotic twins discordant for Crohn’s disease

Background

Crohn’s disease (CD) is an inflammatory bowel disease caused by genetic and environmental factors. More than 160 susceptibility loci have been identified for IBD, yet a large part of the genetic variance remains unexplained. Recent studies have demonstrated genetic differences between monozygotic twins, who were long thought to be genetically completely identical.

Results

We aimed to test if somatic mutations play a role in CD etiology by sequencing the genomes and exomes of directly affected tissue from the bowel and blood samples of one and the blood-derived exomes of two further monozygotic discordant twin pairs. Our goal was the identification of mutations present only in the affected twins, pointing to novel candidates for CD susceptibility loci. We present a thorough genetic characterization of the sequenced individuals but detected no consistent differences within the twin pairs. An estimate of the CD susceptibility based on known CD loci however hinted at a higher mutational load in all three twin pairs compared to 1,920 healthy individuals.

Conclusion

Somatic mosaicism does not seem to play a role in the discordance of monozygotic CD twins. Our study constitutes the first to perform whole genome sequencing for CD twins and therefore provides a valuable reference dataset for future studies. We present an example framework for mosaicism detection and point to the challenges in these types of analyses.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-564) contains supplementary material, which is available to authorized users.     

Utilizing Twins as Controls for Non-Twin Case-Materials in Genome Wide Association Studies

Twin registries around the globe have collected DNA samples from large numbers of monozygotic and dizygotic twins. The twin sample collections are frequently used as controls in disease-specific studies together with non-twins. This approach is unbiased under the hypothesis that twins and singletons are comparable in terms of allele frequencies; i.e. there are no genetic variants associated with being a twin per se. To test this hypothesis we performed a genome-wide association study comparing the allele frequency of 572,352 single nucleotide polymorphisms (SNPs) in 1,413 monozygotic (MZ) and 5,451 dizygotic (DZ) twins with 3,720 healthy singletons. Twins and singletons have been genotyped using the same platform. SNPs showing association with being a twin at P-value < 1 × 10^-5 were selected for replication analysis in 1,492 twins (463 MZ and 1,029 DZ) and 1,880 singletons from Finland. No SNPs reached genome-wide significance (P-value < 5 × 10^-8) in the main analysis combining MZ and DZ twins. In a secondary analysis including only DZ twins two SNPs (rs2033541 close to ADAMTSL1 and rs4149283 close to ABCA1) were genome-wide significant after meta-analysis with the Finnish population. The estimated proportion of variance on the liability scale explained by all SNPs was 0.08 (P-value=0.003) when MZ and DZ were considered together and smaller for MZ (0.06, P-value=0.10) compared to DZ (0.09, P-value=0.003) when analyzed separately. In conclusion, twins and singletons can be used in genetic studies together with general population samples without introducing large bias. Further research is needed to explore genetic variances associated with DZ twinning.