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At least 19 recordsLinked to original sources
PubMed2001

Statistical inferences for a twin correlation with multinomial outcomes.

Current methods for statistical analysis of twin studies focus on continuous and dichotomous data, while only limited methodology exists for analysing multinomial data. As a consequence, investigators are often tempted to collapse multinomial data into two categories simply to facilitate the analysis. We address this problem by developing and evaluating two approaches to the assessment of twin correlation for an outcome variable having more than two nominal categories. One method developed is an extension of the goodness-of-fit approach, while the other method is based on large sample normal theory. Procedures for confidence interval construction are developed and compared using Monte Carlo simulation. The results show that either method may be safely used for confidence interval construction provided the number of twin pairs is large (> or =100) but that in smaller sample sizes the goodness-of-fit procedure is to be preferred on the grounds of validity. Other inference problems are also discussed, including point estimation, hypothesis testing and sample size estimation. An example is included.

Computer Simulation↗
PubMed2003

Genetic and environmental influences on human psychological differences.

Psychological researchers typically distinguish five major domains of individual differences in human behavior: cognitive abilities, personality, social attitudes, psychological interests, and psychopathology (Lubinski, 2000). In this article we: discuss a number of methodological errors commonly found in research on human individual differences; introduce a broad framework for interpreting findings from contemporary behavioral genetic studies; briefly outline the basic quantitative methods used in human behavioral genetic research; review the major criticisms of behavior genetic designs, with particular emphasis on the twin and adoption methods; describe the major or dominant theoretical scheme in each domain; and review behavioral genetic findings in all five domains. We conclude that there is now strong evidence that virtually all individual psychological differences, when reliably measured, are moderately to substantially heritable.

Adoption↗
PubMed2002

The Australian Twin Registry.

The Australian Twin Registry (ATR), established in the late 1970s, is a volunteer registry of over 30,000 pairs of Australian twins of all zygosity types and ages unselected for their health or medical history. The ATR does not undertake research itself but acts as facilitator, providing an important national and international resource for medical and scientific researchers across a broad range of disciplines. Its core functions are the maintenance of an up-to-date database containing basic contact details and baseline information, and the management of access to the resource in ways that enhance research capacity within Australia while protecting the rights of twins. The ATR has facilitated more than 200 studies using a variety of designs, including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. These have yielded more than 300 peer-reviewed publications to date. Areas of major research include studies of behavior, musculoskeletal conditions, teeth and face patterns, cardiovascular risk factors, substance abuse, and risk factors for melanoma and breast cancer. Extensive longitudinal data are available for around 10,000 pairs. DNA samples have been obtained from more than 6000 twins. Considerable efforts are devoted to maintaining the commitment of registry members and recruitment. The ATR hopes to secure funding to expand its activities, including the systematic collection of DNA samples, so that it can continue to play a major role in the development of twin research and contribute to the annotation of the human genome.

Adolescent↗
PubMed2005

Chronic fatigue in a population sample: definitions and heterogeneity.

BACKGROUND: Numerous nosological decisions are made when moving from the common human symptom of unusual fatigue to the rare chronic fatigue syndrome (CFS). These decisions have infrequently been subjected to rigorous evaluation. METHOD: We obtained telephone interview data on fatiguing symptoms from 31406 individuals twins in the Swedish Twin Registry aged 42-64 years; 5330 subjects who endorsed fatigue and possessed no exclusionary condition formed the analytic group. We evaluated the definition and classification of CFS-like illness using graphical methods, regression models, and latent class analysis. RESULTS: Our results raise fundamental questions about the 1994 Centers for Disease Control criteria as (1) there was no empirical support for the requirement of four of eight cardinal CFS symptoms; (2) these eight symptoms were not equivalent in their capacity to predict fatigue; and (3) no combination of symptoms was markedly more heritable. Critically, latent class analysis identified a syndrome strongly resembling CFS-like illness. CONCLUSIONS: Our data are consistent with the 'existence' of CFS-like illness although the dominant nosological approach captures population-level variation poorly. We suggest that studying a more parsimonious case definition - impairing chronic fatigue not due to a known cause - would represent a way forward.

Adult↗
PubMed1996

Risch's lambda values for human obesity.

OBJECTIVE: Risch's lambda statistic (lambda R) is related to the heritability of traits and can be useful in several contexts, including the conduct of power analyses to determine sample size for gene mapping studies. However, values of lambda R have not been presented for human obesity. DESIGN AND RESULTS: Using both analytic and empirical approaches, the present study calculates estimates of lambda R. Examples are provided to illustrate the use of these estimates for determining sample size for genetic mapping studies.

Adolescent↗
PubMed2003

Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies.

CONTEXT: There are many published twin studies of schizophrenia. Although these studies have been reviewed previously, to our knowledge, no review has provided quantitative summary estimates of the impact of genes and environment on liability to schizophrenia that also accounted for the different ascertainment strategies used. OBJECTIVE: To calculate meta-analytic estimates of heritability in liability and shared and individual-specific environmental effects from the pooled twin data. DATA SOURCES: We used a structured literature search to identify all published twin studies of schizophrenia, including MEDLINE, dissertation, and books-in-print searches. STUDY SELECTION: Of the 14 identified studies, 12 met the minimal inclusion criteria of systematic ascertainment. DATA SYNTHESIS: By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%). CONCLUSIONS: Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences. These results are broadly informative in that they provide no information about the specific identity of these etiological influences, but they do provide a component of a unifying empirical basis supporting the rationality of searches for underlying genetic and common environmental etiological factors.

Diseases in Twins↗
PubMed2000

Lack of association of fibrinogen, lipoprotein(a), and albumin excretion rate with low birthweight.

An excess of cardiovascular morbidity has been related to low birthweight. The aim of this study was to evaluate the relationship between low birthweight and levels of fibrinogen, lipoprotein(a), and albumin excretion rate, which are known risk factors for coronary artery disease. Seventy-two twins, with the same within-pair gender and normal glucose tolerance, were analyzed in order to avoid confounding factors, such as gestational age, birth order, or sex. Twins with the highest birthweights within the couple showed no significant difference of fibrinogen, lipoprotein(a), and albumin excretion rates compared with the twins with the lowest birthweights among the two co-twins. Moreover, no relevant correlation was found between birthweight and intra-pair birthweight differences and fibrinogen, lipoprotein(a), and albumin excretion rates. The lack of correlation between fibrinogen, lipoprotein(a), albumin excretion rate and birthweight, suggests that these factors do not contribute to the link between intrauterine malnutrition and increased cardiovascular risk.

Albuminuria↗
PubMed2004

Nature and nurture interplay: schizophrenia.

There is compelling evidence from family, twin and adoption studies of a substantial genetic contribution to schizophrenia. The mode of transmission is complicated and very rarely if ever involves a single gene. Rather schizophrenia results from multiple genes of small effect and their interplay with the environment. Perhaps because the overall size of the genetic effect is large, accounting for about 80 % of variance, definite environmental factors have been difficult to pin down. It has even been suggested that "the environment" consists entirely of epigenetic or stochastic phenomena that can never be detected by a standard epidemiological methods. Nevertheless, a variety of social stressors, including high expressed emotion in relatives and life events affect the course of illness and certain physical factors such as obstetric complications and cannabis smoking have been implicated in contributing to liability to the disorder. The recent discovery of several positional candidate genes that have been replicated as being associated with liability to schizophrenia holds considerable promise not just for a better understanding of the neurobiology but also for improved knowledge about risk prediction and gene-environment interplay.

Diseases in Twins↗
PubMedDate not supplied

Heritability of body height and educational attainment in an international context: comparison of adult twins in Minnesota and Finland.

We studied the effect of genetic and environmental factors on the association between self-reported height and education in Minnesota and Finland. Our data included 1,598 twin pairs in Minnesota and 5,454 twin pairs in Finland born between 1936 and 1955. Correlations between education and height were found in Minnesota (r = 0.09 in men and 0.11 in women) and in Finland (r = 0.17 and 0.14, respectively) after adjustment for age. This trait correlation was mainly because of the correlation between shared environmental factors in Minnesota (r(C) = 0.38 and 0.36, respectively) and in Finland (r(C) = 0.74 and 0.37, respectively). An unshared environmental correlation was found only in Finland (r(E) = 0.13 and 0.06, respectively). Our results indicate that the association between body height and education is overwhelmingly due to the correlation of the shared environmental factors affecting these two traits. The differences between Minnesota and Finland are possibly associated with average higher education in Minnesota, which decreases the effect of the childhood environment on education, seen as a weaker correlation between height and education. Nonfamilial factors affecting education are possibly different in Minnesota than in Finland, since in Finland they are partly associated with the factors affecting height.

Adult↗
PubMed1995

Comparison of analysis of variance and maximum likelihood based path analysis of twin data: partitioning genetic and environmental sources of covariance.

In order to investigate currently used model fitting strategies for twin data, analysis of variance (ANOVA) and path-maximum-likelihood (PATH-ML) methods of analyzing twin data were compared using simulation studies of 50 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs. Phenotypic covariance was partitioned into additive genetic effects (A), environmental effects common to cotwins (C), and environmental variance unique to individuals (E). ANOVA and PATH-ML had identical power to detect total covariance. The PATH-ML AE model was much more powerful than ANOVA comparisons of rMZ and rDZ to detect A. However, to be unbiased, the AE model requires the assumption that C = 0.0. To allow use of the AE model to estimate A, the null hypothesis C = 0.0 is tested by comparing the goodness of fit of the ACE and AE models. Simulation of 50 MZ and 50 DZ pairs revealed that C must be greater than 55% of total variance before the null hypothesis would be rejected (P < 0.05) 80% of the time. Several recent publications were reviewed in which the null hypothesis C = 0.0 was accepted and apparently upwardly biased estimates of A, containing C, were presented with unrealistic P values. It was concluded that use of the AE model to estimate A gives an inflated view of the power of relatively small twin studies. It was recommended that ANOVA or comparison of the ACE and CE PATH-ML models be used to estimate and test the significance of A as neither requires that C = 0.0.

Analysis of Variance↗
PubMed2006

Longitudinal stability of the CBCL-juvenile bipolar disorder phenotype: A study in Dutch twins.

BACKGROUND: The Child Behavior Checklist-juvenile bipolar disorder phenotype (CBCL-JBD) is a quantitative phenotype that is based on parental ratings of the behavior of the child. The phenotype is predictive of DSM-IV characterizations of BD and has been shown to be sensitive and specific. Its genetic architecture differs from that for inattentive, aggressive, or anxious-depressed syndromes. The purpose of this study is to assess the developmental stability of the CBCL-JBD phenotype across ages 7, 10, and 12 years in a large population-based twin sample and to examine its genetic architecture. METHODS: Longitudinal data on Dutch mono- and dizygotic twin pairs (N = 8013 pairs) are analyzed to decompose the stability of the CBCL-JBD phenotype into genetic and environmental contributions. RESULTS: Heritability of the CBCL-JBD increases with age (from 63% to 75%), whereas the effects of shared environment decrease (from 20% to 8%). The stability of the CBCL-JBD phenotype is high, with correlations between .66 and .77 across ages 7, 10, and 12 years. Genetic factors account for the majority of the stability of this phenotype. There were no sex differences in genetic architecture. CONCLUSIONS: Roughly 80% of the stability in childhood CBCL-JBD is a result of additive genetic effects.

Age Factors↗
PubMed2002

Parkinson's disease: current and future challenges.

In 15 years, we will mark the 200th anniversary of the James Parkinson's original description of the disease that now bears his name (An Essay on the Shaking Palsy, Sherwood, Neely and Jones London, 1817). Perhaps, one of the most exciting but daunting questions we face at this moment is whether or not we can unravel the etiology of the disease by that time. If we are to accomplish such an ambitious goal, we must determine the resources that will be required to make it happen, and identify the areas of scientific focus that should receive the greatest attention. One issue that will have great bearing on the allocation of research resources relates to the relative roles of genes versus environment in disease causation. For reasons that will become clear in this article, this has a remained surprisingly controversial area. Ironically, this controversy has even spilled over to the very definition of Parkinson's disease, and even whether or not it should be considered a disease entity. In this article, the enduring "genes versus environment" debate is reviewed, with a goal of putting it into a broader perspective. Issues surrounding disease definition and terminology are also addressed in detail, because of the need to have clarity of thought and vision if research on the cause is to proceed in an orderly (and hopefully expeditious) manner. Finally, issues relating future research directions are summarized, with the goal of identifying the pieces of the Parkinson's puzzle that are going to have to be put together if we are to solve this mysterious disease.

Humans↗
PubMedDate not supplied

Social, biological and reproductive characteristics of mothers of twins: implications for breast cancer risk.

The biological, social and reproductive characteristics of women who have had twins were compared with those of other parous women using questionnaire data gathered for a prospective cohort study of women aged 35 and over on the island of Guernsey. Data for 97 mothers of twins and 4026 other parous women were available for analysis. The two groups were similar in height, first degree family history of breast cancer, use of hormone replacement therapy or other hormones, age at menarche, length of menstrual cycle and age at first and last birth. The mothers of twins were slightly heavier, more likely to smoke and consume more caffeine, less likely to have used oral contraceptives in the past, slightly younger when reaching the menopause and had a larger number of pregnancies. Adjustment for age did not alter these results. This study does not provide evidence that mothers of twins differ markedly from other parous women across a range of characteristics that might be associated with twinning or associated with breast cancer risk.

Adult↗
PubMed2005

Evidence of age-dependent genetic influences on plasma total cholesterol.

BACKGROUND: Causes of variation in cardiovascular risk factors include biological variation within individuals, and more permanent differences between individuals, which are at least partly genetic in origin. We have compared the magnitude of genetic and non-genetic factors within and across occasions through repeated measures of plasma cholesterol in twin subjects, and have also determined how far the same genes affect cholesterol levels at different ages. METHODS: Data on plasma total cholesterol were extracted for 208 twin pairs who had provided blood on up to six occasions across a period of 17 years. They were aged 18-30 years at the time of first study and 30-47 at the time of the last. Multivariate models of variation due to genetic, shared environmental and unique environmental factors were fitted to the multi-occasion data and the proportions of variation due to these factors were estimated. RESULTS: One genetic factor influenced plasma cholesterol on all occasions and a second genetic factor only influenced cholesterol results on the fifth and sixth occasions 10-17 years after the first. Environmental factors did not have significant long-term effects. CONCLUSIONS: We conclude that individuals' long-term mean plasma cholesterol values are strongly genetically determined, but that some of these genes are age-specific in their effects.

Adolescent↗
PubMed2006

Subtypes of illicit drug users: a latent class analysis of data from an Australian twin sample.

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

Australia↗
PubMed2006

Empirical evaluation of the genetic similarity of samples from twin registries in Australia and the Netherlands using 359 STRP markers.

One way to achieve the large sample sizes required for genetic studies of complex traits is to combine samples collected by different groups. It is not often clear, however, whether this practice is reasonable from a genetic perspective. To assess the comparability of samples from the Australian and the Netherlands twin studies, we estimated Fst (the proportion of total genetic variability attributable to genetic differences between cohorts) based on 359 short tandem repeat polymorphisms in 1068 individuals. Fst was estimated to be 0.30% between the Australian and the Netherlands cohorts, a smaller value than between many European groups. We conclude that it is reasonable to combine the Australian and the Netherlands samples for joint genetic analyses.

Australia↗