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Kenneth S. Kendler - One of the best experts on this subject based on the ideXlab platform.
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The Schizophrenia Polygenic Risk Score: To What Does It Predispose in Adolescence?
JAMA psychiatry, 2016Co-Authors: Kenneth S. KendlerAbstract:The initial goal of genome-wide association studies (GWASs) ofpsychiatricdisorderswas to identify individual genetic variants that predispose to illness. Along the way, another application of GWAS data was discovered1: the polygenic risk score (PRS). The concept is simple. We start with all single-nucleotide polymorphisms (SNPs) assessed in a training sample. In this issue of JAMA Psychiatry, Jones et al2 report findings using the second Psychiatric Genomics Consortium schizophrenia GWAS as that sample.3 TheseSNPsarecleanedbyeliminatingones thatare toorare or too highly correlated with their nearest neighbor. The PRS canbeexaminedacross a rangeofPvalue thresholds, as in the first application of thismethod,1 or, as in the study by Jones et al,2 to a single a priori threshold, such as P = .05. For simplicity, imagine that, after cleaning,wehad 1million SNPs distributedacross thegenome inour training sample.Wewould then take the50000SNPs thatmost significantlydiscriminatecases and controls andnote the allele (theA, T, C, orGweall learned about in basic genetics) associatedwith disease risk and its effect size.We then takeour target sample—in this case, thewellknown Avon Longitudinal Study of Parents and Children, a population-based cohort from western England. For each individual, we examine their GWAS data and, for each of our 50000SNPs,determinewhether theyhave0, 1, or 2of the risk alleles. That 0 to 2 score is thenmultiplied by the effect size in the training sample (the logarithm of its odds ratio for schizophrenia) and summed.The total score represents an individual’s PRS for schizophrenia. In this case, because the training set wasso large—andhencerathergoodatseparatingout truefrom false-positive signals—the schizophrenia PRS had, compared withmany other applications of PRSs, a reasonable aggregate effect on adult samples, accounting for approximately 7% of schizophrenia case-control variation on the liability scale. What is soexcitingabout thePRS is that, tomeasure it, you onlyneedDNA(andagood trainingset).Youdonotneed twins or adoptees. You do not need to interview relatives. However, 2 prominent caveats are noteworthy. First, the PRS only reflects thevariationcapturedby the individual commonSNPs used for theGWAS. ThePRSwill not reflect rare SNPs or variation arising from genomic abnormalities (eg, duplications or deletions). Second, thePRS is anaggregatemeasureof risk and does not point to specific variants or any underlying biology. Conceptually, the PRS is therefore similar to the latent genetic variance that psychiatric geneticists have long estimated using twin and adoption designs. Unlike these latent measures, the PRS is assessed fromDNAandnot from resemblance between relatives. However, the PRS is not as predictive because the liability assessed using twin studies indexes all kinds of genomic variants. The PRS also does not have the methodologic concerns of twin studies (eg, Equal Environment Assumption), although it does have several issues of its own that are beyond the scope of this review. What did Jones et al2 find? On a reasonably large sample of adolescents (3676 to 5444 participants), they tried to predict the following from their schizophrenia PRS: (1) positive psychotic experiences, (2) negative symptoms, (3) anxietydisorders, and (4) depression. They found that the schizophrenia PRS significantly predicted negative symptoms and anxiety disorders but not positive psychotic experiences or depression. The effect sizes of their 2 significant results were modest at approximately 1.2 per SD. Therefore, an individual in the top 2.5% of the schizophrenia PRSwould have roughly a 45% increased risk for being in the top decile of negative symptomsorhaving 1 ormore anxietydisorders.What ismost interesting about themethod used in this study is that it provides a new approach to understanding how the genetic risk for schizophreniamanifests itself in adolescence—a question that formed the focus of several high-risk studies of schizophrenia launched a generation or more ago. Let us first focus on the prediction of the 2 key schizophrenia dimensions of positive and negative symptoms. As Jones et al2 point out, their findings closely mirror those reported by Fanous et al4 in adult schizophrenia samples that theschizophreniaPRSsignificantlypredicteddisorganizedand negative symptomsbutnot positive symptoms.Of critical importance, the studyby Joneset al2wasnotperformed inadults with schizophrenia but in a general population of adolescents. The significanceof isolatedpsychotic symptoms ingeneral population samples remains controversial and especially so among adolescents. To their credit, Jones et al2 used an interview-based measure that attempted to confirm the veracity of the symptom,which is likely tobemuchmorevalid than questionnaire-basedmeasures.However, their thresholdwas low, with only 1 confirmed symptom. Recent studies have raised questions about the specificity of isolated psychotic symptoms, suggesting that theymightbeabetter indicator for a broad vulnerability to psychopathology rather than a specific index of schizophrenia.5 The most intriguing result in this study was the relationship between the schizophrenia PRS and negative symptoms. The negative symptom scale used (the Community Assessment of Psychic Experiences [CAPE]) is heterogeneous Related article page 221 Opinion
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illicit psychoactive substance use heavy use abuse and dependence in a us population based sample of male twins
Archives of General Psychiatry, 2000Co-Authors: Kenneth S. Kendler, Michael C Neale, Laura M Karkowski, Carol A. PrescottAbstract:Background In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. Methods In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. Results Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-Environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the Equal Environment Assumption. Conclusions In accord with prior results in studies of women, the family Environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
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Sexual orientation in a U.S. national sample of twin and nontwin sibling pairs.
The American journal of psychiatry, 2000Co-Authors: Kenneth S. Kendler, Laura M. Thornton, Stephen E. Gilman, Ronald C KesslerAbstract:Objective: Although previous studies have suggested that sexual orientation is influenced by familial factors, which may be partly genetic, these studies have relied on unrepresentative and potentially biased samples. The authors attempted to estimate the role of genetic and Environmental factors in the determination of sexual orientation in a more representative sample. Method: Sexual orientation was assessed by a single item on a self-report questionnaire in a U.S. national sample of twin and nontwin sibling pairs. Sexual orientation was classified as heterosexual or nonheterosexual (bisexual or homosexual). The authors compared the similarity of sexual orientation in the monozygotic twins to the similarity in the same-sex dizygotic twins, all dizygotic twins, the same-sex dizygotic twins and sibling pairs, and all dizygotic twins and sibling pairs. Biometrical twin analyses were performed. Results: All analyses demonstrated familial resemblance for sexual orientation. Resemblance was greater in the monozygotic twins than in the dizygotic twins or in the dizygotic twins plus nontwin siblings. Biometrical twin modeling suggested that sexual orientation was substantially influenced by genetic factors, but family Environment may also play a role. No evidence was found for a violation of the Equal-Environment Assumption regarding monozygotic and dizygotic twin pairs. Conclusions: Familial factors, which are at least partly genetic, influence sexual orientation. The results of these analyses should be interpreted in the context of low statistical power and the use of a single item to assess the complex phenotype of sexual orientation.
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a population based twin study of lifetime major depression in men and women
Archives of General Psychiatry, 1999Co-Authors: Kenneth S. Kendler, Carol A. PrescottAbstract:Background Women report higher rates of major depression (MD) than men. Although genetic factors play an important etiologic role in MD, we are uncertain whether genetic factors are of Equal importance in men and women, and whether the same genetic factors predispose men and women to MD. Methods We obtained, by telephone interview, a lifetime history of MD, defined by the DSM-III-R , from 3790 complete male-male, female-female, and male-female twin pairs, identified through a population-based registry. Results were analyzed using probandwise concordance, odds ratios, and biometrical twin modeling. Results The odds ratios (plus tetrachoric correlations) for lifetime MD were as follows: (1) male-male monozygotic, 3.29 (+0.37); (2) male-male dizygotic, 1.86 (+0.20); (3) female-female monozygotic, 3.02 (+0.39); (4) female-female dizygotic, 1.59 (+0.18); and (5) male-female dizygotic, 1.39 (+0.11). In the best-fitting twin model, the heritability of liability to MD was the same in men and women and Equal to 39%, while the remaining 61% of the variance in liability was due to individual-specific Environment. We rejected, with only modest confidence, the hypothesis that the genetic risk factors for MD were the same in men and women. The best-fitting model estimated the genetic correlation in the liability to MD in the 2 sexes to be +0.57. While we found no evidence to suggest a violation of the Equal Environment Assumption, MD was less common in women from opposite-sex vs same-sex twin pairs. Conclusions Major depression is Equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes. However, genes may exist that act differently on the risk for MD in men vs women.
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Heritability of binge-eating and broadly defined bulimia nervosa
Biological psychiatry, 1998Co-Authors: Cynthia M. Bulik, Patrick F. Sullivan, Kenneth S. KendlerAbstract:Abstract Background: Using diagnostic information obtained at two different times, we incorporated error of measurement into structural equation twin models to evaluate the contribution of additive genetic, common Environmental, and individual-specific Environmental factors to the liability to binge-eating and broadly defined bulimia nervosa (BN). We also evaluated the validity of the Equal Environment Assumption (EEA) with reference to these two phenotypes. Methods: We interviewed 1897 female twins (including both members of 854 twin pairs) from a population-based register about their lifetime history of binge-eating and of broadly defined BN twice, approximately 5 years apart. Results: The reliabilities of a lifetime history of binge-eating (κ = .34) and of broadly defined BN (κ = .28) were low. Based on single interviews, the heritability of binge-eating was estimated to be 50% and broad BN 60%, with the remaining variance attributable to individual-specific Environment. Common Environmental influences had no effect on liability to either trait. By combining information from two interview waves and thereby incorporating error of measurement into a structural equation model, the estimated heritability of the latent vulnerability to binge-eating (82%) and broadly defined BN (83%) increased substantially. Although there were no violations of the EEA detected for binge-eating, cosocialization influenced twin concordance for broadly defined BN. Conclusions: Lifetime histories of binge-eating and broadly defined BN appear to be highly heritable conditions of low reliability.
Lindon J Eaves - One of the best experts on this subject based on the ideXlab platform.
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genetic and Environmental factors in relative body weight and human adiposity
Behavior Genetics, 1997Co-Authors: Hermine H Maes, Michael C Neale, Lindon J EavesAbstract:We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent–offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent–offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared Environment, and special twin and MZ twin Environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique Environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin Environment, thereby supporting the Equal Environment Assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.
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Parental treatment and the Equal Environment Assumption in twin studies of psychiatric illness.
Psychological medicine, 1994Co-Authors: Kenneth S. Kendler, M C Neale, Ronald C Kessler, Andrew C Heath, Lindon J EavesAbstract:The validity of the twin method depends on the Equal Environment Assumption (EEA)--that monozygotic (MZ) and dizygotic (DZ) twins are Equally correlated in their exposure to Environmental factors of aetiological importance for the trait under study. Parents may treat MZ twins more similarly than DZ twins thereby potentially violating the EEA. We tested this hypothesis for four common psychiatric disorders (major depression, generalized anxiety disorder, phobia, and alcoholism) in a population-based sample of female-female twin pairs where analyses indicate sufficient statistical power meaningfully to test the EEA. Mother's and father's beliefs about their twins' zygosity disagreed with assigned zygosity in approximately 20% of cases, often because of what they were told about their twins' zygosity at their birth. By structural equation model-fitting, we found no evidence that mother's or father's perceived zygosity influenced twin resemblance for any of the disorders. Compared to parents of DZ twins, parents of MZ twins were more likely to report that, in rearing their twins, they emphasized their similarities more than their differences. However, by model-fitting, mothers' and fathers' approach to raising twins had no significant influence on twin resemblance for the four examined psychiatric disorders. These results suggest that the differential treatment of MZ and DZ twins by their parents is unlikely to represent a significant bias in twin studies of these major psychiatric disorders.
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A longitudinal twin study of 1-year prevalence of major depression in women.
Archives of general psychiatry, 1993Co-Authors: Kenneth S. Kendler, Michael C Neale, Ronald C Kessler, Andrew C Heath, Lindon J EavesAbstract:Objectives: This study seeks to clarify the etiologic importance and temporal stability of the genetic and Environmental risk factors for 1-year prevalence of major depression (1YP-MD) in women. Design: One-year prevalence of major depression was personally assessed, using DSM-III-R criteria, at two time points a minimum of 1 year apart. Participants: Both members of 938 adult femalefemale twin pairs ascertained from the population-based Virginia Twin Registry. Results: The correlation in liability to 1YP-MD was much greater in monozygotic (MZ) than in dizygotic (DZ) twins at time 1 alone, time 2 alone, or at either time 1 or time 2. Model fitting suggested that the liability to 1YP-MD was due to additive genes and individual specific envi- ronment with a heritability of 41% to 46% and was not biased by violations of the Equal Environment Assumption. Jointly analyzing both times of assessment using a longitudinal twin model suggested that, over a 1-year period, genetic effects on the liability to 1YP-MD were entirely stable, while Environmental effects were entirely occasion specific. Conclusions: These results suggest that (1) genetic factors play a moderate etiologic role in the 1YP-MD, (2) the temporal stability of the liability to major depression in adult women is largely or entirely genetic in origin, and (3) Environmental factors play a significant role in the etiology of major depression, but their effects are generally transitory and do not result in enduring changes in the liability to illness.
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a test of the Equal Environment Assumption in twin studies of psychiatric illness
Behavior Genetics, 1993Co-Authors: Kenneth S. Kendler, Michael C Neale, Ronald C Kessler, Andrew C Heath, Lindon J EavesAbstract:The traditional twin method is predicated on the Equal-Environment Assumption (EEA)—that monozygotic (MZ) and dizygotic (DZ) twins are Equally correlated in their exposure to Environmental events of etiologic importance for the trait under study. In 1968, Scarr proposed a test of the EEA which examines the impact of phenotypic similarity in twins of perceived versus true zygosity. We apply this test for the EEA to five common psychiatric disorders (major depression, generalized anxiety disorder, phobia, bulimia, and alcoholism), as assessed by personal interview, in 1030 female-female twin pairs from the Virginia Twin Registry with known zygosity. We use a newly developed model-fitting approach which treats perceived zygosity as a form of specified familial Environment. In 158 of the 1030 pairs (15.3%), one or both twins disagreed with the project-assigned zygosity. Model fitting provided no evidence for a significant influence of perceived zygosity on twin resemblance for any of the five disorders. Although limited in power, these results support the validity of the EEA in twin studies of psychiatric disorders.
Michael C Neale - One of the best experts on this subject based on the ideXlab platform.
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illicit psychoactive substance use heavy use abuse and dependence in a us population based sample of male twins
Archives of General Psychiatry, 2000Co-Authors: Kenneth S. Kendler, Michael C Neale, Laura M Karkowski, Carol A. PrescottAbstract:Background In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. Methods In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. Results Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-Environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the Equal Environment Assumption. Conclusions In accord with prior results in studies of women, the family Environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
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genetic and Environmental factors in relative body weight and human adiposity
Behavior Genetics, 1997Co-Authors: Hermine H Maes, Michael C Neale, Lindon J EavesAbstract:We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent–offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent–offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared Environment, and special twin and MZ twin Environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique Environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin Environment, thereby supporting the Equal Environment Assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.
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Physical similarity and the Equal-Environment Assumption in twin studies of psychiatric disorders
Behavior Genetics, 1995Co-Authors: John M. Hettema, Michael C Neale, Kenneth S. KendlerAbstract:The Equal-Environment Assumption (EEA), upon which twin methodology is based, was examined for the impact of physical similarity on phenotypic resemblance in five common psychiatric disorders: major depression, generalized anxiety disorder, phobia, alcoholism, and bulimia. A population-based sample of 882 female-female twin pairs of known zygosity was rated for similarity of appearance by color photographs. Psychiatric diagnoses were made by clinical assessment of personal interviews of the twins. Structural equation modeling of the data using physical similarity as a form of specified common Environment provided no evidence for a significant effect of physical resemblance on concordance for major depression, generalized anxiety disorder, phobia, and alcoholism, thereby supporting the validity of the EEA in twin studies of these disorders. Results for bulimia, on the other hand, suggest, within the limitations of this study, that physical similarity may significantly influence twin resemblance for this disorder.
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A longitudinal twin study of 1-year prevalence of major depression in women.
Archives of general psychiatry, 1993Co-Authors: Kenneth S. Kendler, Michael C Neale, Ronald C Kessler, Andrew C Heath, Lindon J EavesAbstract:Objectives: This study seeks to clarify the etiologic importance and temporal stability of the genetic and Environmental risk factors for 1-year prevalence of major depression (1YP-MD) in women. Design: One-year prevalence of major depression was personally assessed, using DSM-III-R criteria, at two time points a minimum of 1 year apart. Participants: Both members of 938 adult femalefemale twin pairs ascertained from the population-based Virginia Twin Registry. Results: The correlation in liability to 1YP-MD was much greater in monozygotic (MZ) than in dizygotic (DZ) twins at time 1 alone, time 2 alone, or at either time 1 or time 2. Model fitting suggested that the liability to 1YP-MD was due to additive genes and individual specific envi- ronment with a heritability of 41% to 46% and was not biased by violations of the Equal Environment Assumption. Jointly analyzing both times of assessment using a longitudinal twin model suggested that, over a 1-year period, genetic effects on the liability to 1YP-MD were entirely stable, while Environmental effects were entirely occasion specific. Conclusions: These results suggest that (1) genetic factors play a moderate etiologic role in the 1YP-MD, (2) the temporal stability of the liability to major depression in adult women is largely or entirely genetic in origin, and (3) Environmental factors play a significant role in the etiology of major depression, but their effects are generally transitory and do not result in enduring changes in the liability to illness.
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A pilot Swedish twin study of affective illness, including hospital- and population-ascertained subsamples.
Archives of general psychiatry, 1993Co-Authors: Kenneth S. Kendler, Michael C Neale, Nancy L. Pedersen, Lars Johnson, Aleksander A. MathéAbstract:Objective: We sought to compare the probandwise concordance rate (PRC) for affective illness (AI) in monozygotic (MZ) and dizygotic (DZ) twins in samples ascertained through psychiatric hospitalization vs samples from the general population. Methods: Twins were ascertained through psychiatric hospitalization for AI from the Swedish Psychiatric Twin Registry or as a matched sample from the population-based Swedish Twin Registry. Lifetime diagnoses were based on a mailed questionnaire containing, in self-report format, DSM-III-R criteria for mania and major depression. Returned questionnaires were obtained from 1484 individuals and both members of 486 pairs, of whom 154 were classified as MZ, 326 as DZ, and six of unknown zygosity. Results: No evidence was found for violations of the Equal Environment Assumption. Using either a narrow or broad diagnostic approach, the risk for AI in cotwins of proband twins was independent of the gender, polarity (ie, unipolar vs bipolar) and mode of ascertainment of the affected proband (ie, via hospitalization vs from the general population). Combining both subsamples, PRC for total AI using narrow diagnostic criteria was 48.2% in MZ and 23.4% in DZ twins. Using broad diagnostic criteria, the parallel figures were 69.7% and 34.9%. The risk for bipolar illness was substantially increased in the cotwins of probands with bipolar AI. Conclusions:
Carol A. Prescott - One of the best experts on this subject based on the ideXlab platform.
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illicit psychoactive substance use heavy use abuse and dependence in a us population based sample of male twins
Archives of General Psychiatry, 2000Co-Authors: Kenneth S. Kendler, Michael C Neale, Laura M Karkowski, Carol A. PrescottAbstract:Background In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. Methods In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. Results Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-Environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the Equal Environment Assumption. Conclusions In accord with prior results in studies of women, the family Environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
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Chorion type as a possible influence on the results and interpretation of twin study data.
Twin research : the official journal of the International Society for Twin Studies, 1999Co-Authors: Carol A. Prescott, Ronald C. Johnson, John J. McardleAbstract:The estimation of genetic effects from twin studies usually relies upon the Equal Environment Assumption--that monozygous (MZ) and dizygous (DZ) twin pairs experience Equal similarity of their Environments from prenatal experiences through adulthood. However, the sharing of a chorion may make a subset of identical twins more similar, or in some cases, more different, than twins that do not share a chorion. Recent studies suggest monochorionic MZ twins resemble one another more than dichorionic MZ twins in cognitive abilities, personality, and risk for psychiatric disorder. To the extent that prenatal Environment affects these characteristics, the traditional twin method will yield biased estimates of genetic and Environmental influences. We develop models for quantifying this bias and estimating the influence of chorion type on estimates of heritability.
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a population based twin study of lifetime major depression in men and women
Archives of General Psychiatry, 1999Co-Authors: Kenneth S. Kendler, Carol A. PrescottAbstract:Background Women report higher rates of major depression (MD) than men. Although genetic factors play an important etiologic role in MD, we are uncertain whether genetic factors are of Equal importance in men and women, and whether the same genetic factors predispose men and women to MD. Methods We obtained, by telephone interview, a lifetime history of MD, defined by the DSM-III-R , from 3790 complete male-male, female-female, and male-female twin pairs, identified through a population-based registry. Results were analyzed using probandwise concordance, odds ratios, and biometrical twin modeling. Results The odds ratios (plus tetrachoric correlations) for lifetime MD were as follows: (1) male-male monozygotic, 3.29 (+0.37); (2) male-male dizygotic, 1.86 (+0.20); (3) female-female monozygotic, 3.02 (+0.39); (4) female-female dizygotic, 1.59 (+0.18); and (5) male-female dizygotic, 1.39 (+0.11). In the best-fitting twin model, the heritability of liability to MD was the same in men and women and Equal to 39%, while the remaining 61% of the variance in liability was due to individual-specific Environment. We rejected, with only modest confidence, the hypothesis that the genetic risk factors for MD were the same in men and women. The best-fitting model estimated the genetic correlation in the liability to MD in the 2 sexes to be +0.57. While we found no evidence to suggest a violation of the Equal Environment Assumption, MD was less common in women from opposite-sex vs same-sex twin pairs. Conclusions Major depression is Equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes. However, genes may exist that act differently on the risk for MD in men vs women.
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A population-based twin study of self-esteem and gender
Psychological medicine, 1998Co-Authors: Kenneth S. Kendler, Charles O. Gardner, Carol A. PrescottAbstract:Background. Self-esteem (SE), a widely used construct in the social sciences, is usually conceptualized as a reflection of socialization and interpersonal experiences that may differ considerably between the genders. Methods. The Rosenberg self-esteem scale was assessed at personal interview in both members of 3793 unselected twin pairs (1517 male–male, 856 female–female and 1420 male–female) from the population-based Virginia Twin Registry. Gender effects on SE were assessed by both analysis of variance and biometrical twin modelling. Results. The mean SE score was slightly but significantly lower in women v . men, and in women who grew up with a male v . a female co-twin. Twin modelling suggested that: ( i ) individual differences in self-esteem in both men and women were best explained by genetic and individual-specific Environment factors; ( ii ) heritability estimates were similar in women (32%) and in men (29%); and ( iii ) the same genetic factors that influenced SE in women also influenced SE in men. Analyses supported the validity of the Equal Environment Assumption for SE. The heritability of SE cannot be explained by the moderate correlation between SE and symptoms of depression. Conclusions. These results are inconsistent with prominent gender-related aetiological models for SE, which postulate that individual differences arise from socialization experiences both within and outside the home of origin which differ widely for the two genders. Instead, a significant proportion of the population variance in SE is due to genetically-influenced temperamental variables that are the same in men and women.
Jay Joseph - One of the best experts on this subject based on the ideXlab platform.
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Schizophrenia: A critical view on genetic effects
Psychosis, 2015Co-Authors: Roar Fosse, Jay Joseph, Mike JonesAbstract:The main justification for molecular genetics studies of enduring psychosis (schizophrenia) are high heritability estimates obtained from classical twin studies. The classical twin method rests upon the Equal Environment Assumption (EEA), which holds that reared-together identical and fraternal twin pairs grow up experiencing Equally similar Environmental exposures. However, a review of prior twin studies shows that identical twins are more similar than fraternal twins on childhood exposures that are central to the etiology of psychosis. Such exposures include bullying, sexual abuse, physical maltreatment, emotional neglect and abuse, and general trauma. An additional Assumption presented by twin researchers, that the differential intraclass correlation for child social adversities can be explained by evocative gene–Environment covariation, is not consistent with the available evidence. Moreover, due to an array of methodological problems and questionable Assumptions, adoption studies provide misleading i...
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A Critical Assessment of the Equal-Environment Assumption of the Twin Method for Schizophrenia
Frontiers in psychiatry, 2015Co-Authors: Roar Fosse, Jay Joseph, Ken RichardsonAbstract:The classical twin method (CTM) is central to the view that schizophrenia is ~80% heritable. The CTM rests on the Equal Environments Assumption (EEA) that identical and fraternal twin pairs experience equivalent trait relevant Environmental exposures. The EEA has not been directly tested for schizophrenia with measures of child social adversity, which is particularly etiologically relevant to the disorder. However, if child social adversity is more similar in identical than fraternal pairs in the general twin population, the EEA is unlikely to be valid for schizophrenia, a question which we tested in this study. Using results from prior twin studies, we tested if intraclass correlations for the following five categories of child social adversity are larger in identical than fraternal twins: bullying, sexual abuse, physical maltreatment, emotional neglect and abuse, and general trauma. Eleven relevant studies that encompassed 9119 twin pairs provided 24 comparisons of intraclass correlations, which we grouped into the five social exposure categories. Fisher’s z-test revealed significantly higher correlations in identical than fraternal pairs for each exposure category (z ≥ 3.53, p
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a critical assessment of the Equal Environment Assumption of the twin method for schizophrenia
Frontiers in Psychiatry, 2015Co-Authors: Roar Fosse, Jay Joseph, Ken RichardsonAbstract:The classical twin method (CTM) is central to the view that schizophrenia is ~80% heritable. The CTM rests on the Equal Environments Assumption (EEA) that identical and fraternal twin pairs experience equivalent trait relevant Environmental exposures. The EEA has not been directly tested for schizophrenia with measures of child social adversity, which is particularly etiologically relevant to the disorder. However, if child social adversity is more similar in identical than fraternal pairs in the general twin population, the EEA is unlikely to be valid for schizophrenia, a question which we tested in this study. Using results from prior twin studies, we tested if intraclass correlations for the following five categories of child social adversity are larger in identical than fraternal twins: bullying, sexual abuse, physical maltreatment, emotional neglect and abuse, and general trauma. Eleven relevant studies that encompassed 9119 twin pairs provided 24 comparisons of intraclass correlations, which we grouped into the five social exposure categories. Fisher’s z-test revealed significantly higher correlations in identical than fraternal pairs for each exposure category (z ≥ 3.53, p <.001). The difference remained consistent across gender, study site (country), sample size, whether psychometric instruments were used, whether interviewing was proximate or distant to the exposures, and whether informants were twins or third persons. Combined with other evidence that the differential intraclass correlation for child social adversity cannot be explained by evocative gene-Environment covariation, our results indicate that the CTM does not provide any valid indication of genomic effects in schizophrenia.
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The Genetics of Political Attitudes and Behavior: Claims and Refutations
Ethical Human Psychology and Psychiatry, 2010Co-Authors: Jay JosephAbstract:Some political scientists have argued in recent years that twin research shows that genetic factors play an important role in shaping political attitudes, ideologies, and behavior. Moreover, some researchers claim to have identified genes for political traits at the molecular level. The author argues that the main theoretical Assumption of the twin method, which holds that monozygotic and dizygotic twin pairs experience Equal Environments, is untenable. Therefore, the results of twin studies can be completely explained by nongenetic factors. The author also argues that recent gene discovery claims in political science are unlikely to be replicated. He concludes that because genetic interpretations of twin study results are confounded by Environmental factors, political scientists have no reason to revise previous socialization theories of political traits. Keywords: behavioral genetics; Equal Environment Assumption; genetics; political science; twin study; molecular genetics; voting Since at least 2005, political scientists Alford, Funk, and Hibbing (2005) and others have argued that differences in political orientation and behavior have an important genetic basis (others making such claims include Alford, Funk, & Hibbing, 2008a, 2008b; Bell, Shermer, & Vernon, 2009; Fowler, Baker, & Dawes, 2008; Fowler & Dawes, 2008; Hatemi, Alford, Hibbing, Martin, & Eaves, 2009; Hatemi, Medland, & Eaves, 2009; Hatemi, Medland, Morely, Heath, & Martin, 2007; Medland & Hatemi, 2009; Hatemi et al., 2010). Intuitively, we might reject such an idea out of hand, yet the past few years have seen claims that the link between genes and political behavior and attitudes has been established by twin research. This has led to the creation of the nascent field of "genopolitics" and to the claim that there is a "developing consensus that genes play an important role in political behavior" (Settle, Dawes, & Fowler, 2009, p. 601). It is my understanding that political scientists take quantitative empirical methodology very seriously. Thus, one can only welcome a thorough evaluation of twin research by this field. This does not usually occur in psychiatry and psychology, where journals regularly publish the results of behavioral genetic research with little or no critical analysis. Conversely, genetic theories and claims have sparked a debate in political science on the validity of twin research (for criticism of twin research in political science, see Beckwith & Morris, 2008; Charney, 2008a, 2008b, 2010; Suhay, Kalmoe, & McDermott, 2007; for responses to these critics, see Alford et al., 2008a, 2008b; Hannagan & Hatemi, 2008). What concerns us here is the possible role of genetic influences on individual differences in political attitudes and behavior, not the undisputed fact that human beings are the product of both their genes and their Environments. Political scientists Hannagan and Hatemi (2008) stated the obvious when they wrote, mistakenly implying that critics of genetic research disagree, "The scientific community recognizes that genes are very much a part of what it means to be human" (p. 332). We might as well say that the scientific community recognizes that Barack Obama won the 2008 U.S. presidential election. Human behavioral genetic researchers, however, are concerned with trait variation in the population and usually conclude that heredity plays an important role in explaining this variation. In their twin study, Alford et al. (2005) concluded that "genetics plays an important role in shaping political attitudes and ideologies" (p. 153). They reached this conclusion on the basis of finding a significantly higher correlation of MZ (monozygotic, identical) versus same-sex DZ (dizygotic, fraternal) twin pairs on Wilson-Patterson Attitude Inventory scores. They used the "classical twin method" (hereafter the "twin method"; political science twin researchers sometimes refer to the twin method as the "classical twin design"). …
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Twin studies in psychiatry and psychology: science or pseudoscience?
The Psychiatric quarterly, 2002Co-Authors: Jay JosephAbstract:Twin studies are frequently cited in support of the influence of genetic factors for a wide range of psychiatric conditions and psychological trait differences. The most common method, known as the classical twin method, compares the concordance rates or correlations of reared-together identical (MZ) vs. reared-together same-sex fraternal (DZ) twins. However, drawing genetic inferences from MZ–DZ comparisons is problematic due to methodological problems and questionable Assumptions. It is argued that the main theoretical Assumption of the twin method—known as the “Equal Environment Assumption”—is not tenable. The twin method is therefore of doubtful value as an indicator of genetic influences. Studies of reared-apart twins are discussed, and it is noted that these studies are also vulnerable to methodological problems and Environmental confounds. It is concluded that there is little reason to believe that twin studies provide evidence in favor of genetic influences on psychiatric disorders and human behavioral differences.