0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Heritability of Autistic Traits in the General Population FREE

Rosa A. Hoekstra, MSc; Meike Bartels, PhD; Catharina J. H. Verweij, MSc; Dorret I. Boomsma, PhD
[+] Author Affiliations

Author Affiliations: Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.


Arch Pediatr Adolesc Med. 2007;161(4):372-377. doi:10.1001/archpedi.161.4.372.
Text Size: A A A
Published online

Objective  To explore genetic and environmental influences on individual differences in autistic traits in early adulthood and to test if there is assortative mating (nonrandom partner choice) for autistic traits in the general population.

Design  Twin family study using structural equation modeling.

Setting  Population-based twin family sample from the Netherlands.

Participants  Twins aged 18 years (n = 370) and their siblings (n = 94); parents of twins (128 couples).

Main Outcome Measure  Self-reported Autism-Spectrum Quotient (AQ) scores, a quantitative measure of autistic traits.

Results  Autistic traits were continuously distributed in the population. Twins and siblings did not significantly differ in AQ scores; men obtained significantly higher AQ scores than women (in twin-sibling sample, P<.001; twin-parent sample, P = .02). Individual differences in endorsement on autistic traits show substantial heritability (57%). No significant shared environmental influences were detected. The genes affecting autistic traits appear to be the same across the sexes. The correlation in AQ score between spouses was low and not significant (Pearson r = .05; P = .59).

Conclusions  Previous general population twin studies reported high heritability for autistic traits in childhood and early adolescence. This study extends these findings to late adolescence and yields no evidence for sex-specific genetic influences on autistic traits in later stages of development. As autistic traits show substantial variation in the general population, future genetic studies may be facilitated by measuring autistic traits on a continuous scale like the AQ. No evidence for assortative mating for autistic traits was found, suggesting that, in the general population, there is no passive or active partner selection for autistic traits.

Figures in this Article

Autism spectrum disorders (ASDs) are characterized by a triad of features: (1) difficulties with social interaction, (2) difficulties with communication, and (3) the presence of restricted repetitive and stereotyped patterns of behavior, interests, and activities.1 Twin and family studies have shown that ASDs are highly heritable.2 While the concordance of autism in monozygotic twins is 60% to 90%, concordance in dizygotic twins is only 0% to 5%,3,4 which results in a heritability estimate above 90%.2 Moreover, relatives of individuals with autism show increased rates of social deficits, impairments in communication and language, a preference for routines, and difficulty with change.48

Rather than treating autism as a distinct disorder, recent studies have used a dimensional approach to study autistic traits.9,10 These studies suggest that ASDs represent the upper extreme of a constellation of traits that may be continuously distributed in the population.7,911 Studies quantifying autistic traits have found elevated scores in relatives of people with an ASD12,13 and in children whose parents showed high (but subdiagnosed) endorsement on autistic traits.14

The dimensional approach has also been incorporated in twin studies. A study in 7- to 15-year-old twins using the Social Responsiveness Scale yielded mixed results.9,15 A first report in only male twins suggested strong heritability (76%), no shared environmental influences, and moderate nonshared environmental influences (24%).15 In a subsequent report also including female and opposite-sex twin pairs, heritability decreased to 48%, and both significant shared (32%) and nonshared (20%) environmental influences were found.9 In more than 3000 7-year-old male, female, and opposite-sex twin pairs, both social and nonsocial autistic behaviors were found to be highly heritable.16 A study in the same sample 1 year later reported high heritability of autistic traits and no shared environmental influences.17 The latter study also used a categorical approach (extreme vs typical endorsement on autistic traits) and found results similar to the dimensional approach, yielding no indication that etiology is different at the extreme end of the spectrum. These studies were all conducted in children and young adolescents. No studies of the heritability of autistic traits at later ages have been reported yet, and none have included siblings of twins. Furthermore, the studies mentioned were all based on parent or teacher ratings. Previous studies of behavioral problems have shown that external and self-rated reports may yield other results, as different raters can provide different perspectives on behavior.16,18,19 Our study aims to examine genetic and environmental influences on self-reported autistic traits in a sample of 18-year-old twins and their siblings using the Autism-Spectrum Quotient (AQ),10 a well-validated instrument used to quantify autistic traits (R.A.H., unpublished data, 2006).

Additionally, assortative mating (nonrandom partner choice) for autistic traits will be examined. Assortative mating for traits related to autism has been proposed as a risk factor for having a child with autism.20 Moreover, if present in the general population, assortative mating could influence the frequency of the genotypes related to autistic traits and bias correlations in first-degree relatives and, consequently, heritability estimates. One previous study of assortative mating for autistic traits reported a spouse correlation of r = 0.38.14 However, in this study, spouses rated each other and not themselves on the endorsement of autistic traits. Shared beliefs or perceptions about the couple's relationship may have inflated the results. Various studies have explored partner resemblance for personality traits and reported modest to moderate similarity for introversion2123 and modest similarity in preference for consistency and routine.23 We examined assortative mating for autistic traits in a general population sample using self-reported AQ scores.

PARTICIPANTS

The twin families participating in the heritability study were recruited via the Netherlands Twin Register kept by the Department of Biological Psychology at the VU University in Amsterdam.24,25 The current study sample comprised 194 families and is part of an ongoing longitudinal project examining development of cognition and behavioral problems. Participation rate for this data collection was 54%. Participating families did not significantly differ from nonparticipating families in socioeconomic status (Mann-Whitney test, U = 10382.00; P = .23; effect size, r = 0.07), but parental education level was slightly higher in participating families (education of mother, U = 9538.00, P = .05, r = 0.12; father, U = 7773.00, P = .01, r = 0.16). No information about ASD diagnoses was available. Mean age of the twins was 18.18 years (SD, 0.22; range, 17.61-18.99); mean sibling age was 18.77 years (SD, 4.71; range, 10.52-35.39). Most twin families (n = 184) completed the AQ in the university laboratory as part of an extensive test protocol. The other families (n = 10) filled out the questionnaire at home. The sample consisted of 36 monozygotic male twin pairs, 35 dizygotic male twin pairs, 45 pairs of monozygotic female twins, 39 pairs of dizygotic female twins, and 39 dizygotic twin pairs of opposite sex. Zygosity of the same-sex twin pairs (n = 155) was determined by DNA analyses (n = 101), blood group polymorphisms (n = 45), or discriminant analyses of longitudinally collected questionnaire items (n = 9). This method has been proven to be of sufficient reliability.26 This study was approved by the Central Committee on Research Involving Human Subjects and the institutional review board of the VU University Amsterdam. Written informed consent was obtained from all participating subjects.

To study assortative mating for autistic traits, parents of twins (unrelated to the twin families mentioned) were asked to fill out the AQ during an informational day for parents of multiples. They either completed the AQ during the day or returned it to our research group by mail. The response rate was 62%; no information was available about nonresponders. The mean age of the participants was 35.68 years (SD, 6.33). Only data of male-female couples were included; complete partner data on the AQ were available for 128 pairs. All couples were either living together or married.

DUTCH AUTISM-SPECTRUM QUOTIENT

The AQ consists of 50 items assessing personal preferences and habits. Subjects rate to what extent they agree or disagree with the statements on a 4-point Likert scale, with the following answer categories: 1 representing definitely agree; 2, slightly agree; 3, slightly disagree; and 4, definitely disagree. Total AQ scores were calculated as the sum of the Likert scale scores. For items in which an agree response was characteristic for autism, the scoring was reversed (definitely agree scored 4 points; slightly agree, 3 points; slightly disagree, 2 points; and definitely disagree, 1 point). The minimum AQ score (50) indicates no autistic traits; the maximum score (200) suggests full endorsement on all autistic items.

The original English version of the AQ10 was translated into Dutch using a backward translation procedure. After comparing the outcome of the retranslated version with the original text, a final version was established. The Dutch translation of the AQ has good internal consistency (Cronbach α = 0.79) and test-retest reliability (Pearson r = 0.78 in a group of 75 subjects with a 1- to 6-month time interval) (R.A.H., unpublished data, 2006).

If more than 5 items were left blank, the AQ was considered incomplete and the data were discarded in subsequent analyses (n = 7 in the twin-sibling sample). Complete AQs were available for 370 twins and 94 siblings. If 5 or fewer answers were missing, the AQ score was corrected for the number of missing items by making the following calculation: total AQ score + (mean item score × number of missing items). Twenty-one individuals were missing 1 answer, and 3 individuals were missing 2 answers.

DATA ANALYSES

Descriptive statistics were calculated using SPSS 13.0 for Windows (SPSS Inc, Chicago, Ill). Twin-sibling differences in AQ score and effects of birth order, zygosity, age, and sex were examined using a saturated model in the structural equation modeling program Mx.27 Twin and twin-sibling correlations for AQ scores were estimated for each zygosity group. Sex differences in mean AQ score in the twin-parent sample were examined using analysis of variance. Assortative mating was studied by calculating the Pearson correlation between AQ scores of spouses.

Because monozygotic twins are genetically identical, while dizygotic twins and siblings share on average 50% of their segregating genes, genetic modeling of twin-sibling data allows decomposing of the observed phenotypic variance into genetic and environmental components (Figure 1). Additive genetic influences result from the additive effects of alleles at all contributing genetic loci. Shared environmental influences result from environmental effects common to all members of the family. Nonshared environmental influences represent environmental factors unique to each family member and also include measurement error. These variance components were estimated by using Mx.27 The fit of various models was compared using a likelihood ratio test, which is the difference between minus twice the log likelihoods under 2 nested models and is distributed as a χ2. The df are given as the difference in the number of parameters estimated in the 2 models. A high increase in χ2 against a low gain of df denotes a worse fit of a submodel compared with the full model. The most parsimonious model was chosen as the best model. Analyses were performed on the raw data. The significance of sex differences in the variance components was tested by examining the deterioration in model fit after constraining the magnitude of additive genetic influences, shared environmental influences, and nonshared environmental influences to be equal across the sexes. The significance of the contribution of additive genetic influences and shared environmental influences was tested by assessing the deterioration in model fit after each component was dropped from the full model.

Place holder to copy figure label and caption
Figure 1.

Univariate path diagram representing the contribution of additive genetic (A), shared environmental (C), and nonshared environmental (E) influences to the trait under investigation (Autism-Spectrum Quotient scores). The factor loadings of these influences are represented by a, c, and e. The correlation of the additive genetic factors is 1.0 in monozygotic twins and, on average, 0.5 in dizygotic twins and between twins and siblings. The correlation of the shared environmental effects is 1.0 between twins and between twins and siblings. E represents effects unique to a family member and are thus uncorrelated.

Graphic Jump Location

Table 1 presents the descriptive statistics for AQ scores in the twins and their siblings, and in spouses drawn from the sample of parents of twins. Autism-Spectrum Quotient scores were continuously distributed (Figure 2). No differences in mean AQ scores between twins and siblings were found (102.1 vs 102.9, respectively; χ21 = 1.18; P = .28). Moreover, no effects of birth order (χ22 = 1.66; P = .44), zygosity (χ21 =1.44; P = .23), or age (χ21 = 0.59; P = .44) could be detected. A significant sex effect on the mean was found; mean AQ scores were significantly higher in men than in women (104.0 vs 100.8, respectively; χ21 = 12.97; P<.001; effect size, d = 0.30). Similarly, in the twin-parent sample, men obtained significantly higher AQ scores than women (mean 106.0 vs 102.8, respectively; F1,254 = 5.32; P = .02; d = 0.28). No evidence for assortative mating for autistic traits was found. The partner correlation for AQ score was r = 0.05 (P = .59).

Place holder to copy figure label and caption
Figure 2.

Distribution of Autism-Spectrum Quotient (AQ) scores in twins and their siblings.

Graphic Jump Location
Table Graphic Jump LocationTable 1. Sample Size and AQ Score in Twins, Their Siblings, and in Spouses

Twin and twin-sibling correlations are presented in Table 2. Inspection of the monozygotic, dizygotic, and twin-sibling correlations gives a first impression of what factors influence individual differences in AQ scores. Although the confidence intervals overlap, the estimates for monozygotic correlations are higher than dizygotic and twin-sibling correlations, indicating that genetic factors may play a role. As twin correlations in opposite-sex twins are not attenuated, compared with the correlations in same-sex dizygotic twins, there is no indication for sex-specific genes influencing variance in AQ scores. The monozygotic correlations are not twice as high as the dizygotic correlations and twin-sibling correlations, suggesting that shared environmental factors could also be of importance.

Table Graphic Jump LocationTable 2. Twin and Twin-Sibling Correlations

Model-fitting statistics for the full model, including both additive genetic, shared environmental, and nonshared environmental influences (referred to as the ACE model), and various submodels are presented in Table 3. Constraining the parameters that represent the effect of additive genetic, shared environmental, and nonshared environmental influences as equal across the sexes did not significantly worsen the fit (χ23 = 2.88; P = .41), confirming that the relative effects of these components were the same in men and women. Dropping the shared environmental component from the model did not result in a worse model fit (χ21 = 0.78; P = .37). The genetic effects, however, were of significant importance (χ21 = 4.35; P = .04). In the best-fitting parsimonious model, individual differences in autistic traits were explained by additive genetic influences (accounting for 57% of the variance) and nonshared environmental effects (accounting for 43% of the variance).

Table Graphic Jump LocationTable 3. Model Fit Statistics and Parameter Estimates for the Best-Fitting Model

The present study shows that autistic traits, as measured by the AQ in the general population, are continuously distributed; show a significant sex difference in mean scores, with men scoring higher than women; and are unrelated to age or to being born a twin or singleton. Moreover, individual differences in autistic traits show substantial heritability, and are influenced by the same additive genetic factors in men and women. No evidence for assortative mating for autistic traits was found.

The finding of a significant sex difference in mean AQ scores in both the twin-sibling and the twin-parent sample is in concordance with findings using other measures of autistic traits, such as the Social Responsiveness Scale9 and Childhood Asperger Syndrome Test,17 and with earlier studies using the AQ from the United Kingdom and Japan,10,28 suggesting cross-cultural similarities. All studies report higher endorsement on autistic traits in men than in women, which is in line with the observation that ASDs are more common in men than in women.29

We did not find a difference in mean AQ scores between twins and singletons. Some studies have suggested the process of twinning as a risk factor for the development of autism.30,31 Large population-based studies did not support these findings.3234 Our results indicate that in the general population, endorsement of autistic traits is unrelated to being born a twin or singleton.

In 18-year-old twins and their siblings, variance in autistic traits is largely explained by additive genetic effects (57%). Shared environmental effects were not of significant importance; nonshared environmental effects accounted for 43% of the variance. Twin correlations in same-sex dizygotic twins were of similar magnitude as the correlation in opposite-sex twins, yielding no evidence for sex-specific genes for autistic traits. Comparable dizygotic same-sex and opposite-sex twin correlations were found in twin studies in childhood and early adolescence.9,16,17 Our results indicate that even in more advanced stages of development, the set of genes influencing autistic traits is the same across the sexes.

The correlations in first-degree relatives in this study ( = 0.32) are similar to the dizygotic twin correlations reported in other studies assessing autistic traits on a continuum9,16,17 but are considerably larger than dizygotic twin concordance rates and sibling prevalence rates for clinical diagnosis of autism (0%-5%).24,35 It is found that dizygotic twin concordance rates and sibling prevalence increase when diagnostic criteria are relaxed and include a broader phenotype of autistic traits.48 It may be that first-degree relative correlations in clinical samples increase even more when autistic traits are measured on a continuous scale such as the AQ. Although tentative, these findings may have implications for genetic studies, as the strong disparity between monozygotic and dizygotic twin concordance rates for diagnosed autism have led to the hypothesis that gene-gene interactions play an important role in the risk for autism.

Our results suggest that shared environmental effects are not of major importance in explaining the variance of autistic traits, but the power to detect such effects was limited with our sample size.36 In previous studies including larger sample sizes, 1 study found no shared environmental effects,17 1 reported a small but significant contribution of shared environment in girls but not in boys,16 and 1 reported moderate shared environmental influences in both sexes.9 The studies reporting significant shared environmental effects were both based on parental reports. As the parent rates the behavior of both members of the twin pair, rater bias may have inflated the shared environmental effects in these studies.

Our study relied on self-report measurement of autistic traits. As subjects with autism may underestimate their social impairment, the AQ asks about preferences rather than behavioral judgments. Previous studies have indicated that the AQ is a valid instrument to assess autistic traits (R.A.H., unpublished data, 2006).10 However, the agreement between self-ratings and other ratings of autistic traits is as yet unexplored. Future studies should include multiple raters of autistic behavior to account for rater bias and rater-specific views, as previous studies have shown that different raters can provide substantial additional information.16,37 No information about ASD diagnoses was available in this study, and the sample included few extreme scorers on the AQ. Previous studies yielded no evidence that the etiology of autistic traits is different in the general population vs the extreme. However, the real test for this should come from genetic studies.

No evidence for assortative mating for autistic traits was found. The correlation of AQ scores between partners was close to zero. This is in contrast to a previous study that reported a spouse correlation of r = 0.38.14 However, as their assessment of autistic traits was based on spouse report, shared perceptions about the relationship may have inflated the correlation.14 All participants in our assortative mating study were recruited on an informational day for parents of multiples. Individuals who dislike being confronted with large crowds may be unlikely to attend this event. Our sample may therefore not be completely representative of the general population. The results suggest that in the general population, people do not actively or passively select their partner for autistic characteristics. One theory has proposed assortative mating for extreme autistic traits as a risk factor for having a child with an ASD.20 Our sample included insufficient numbers of extreme AQ scorers to test this hypothesis.

From these data, we conclude that variance in autistic traits, as measured with the AQ, show substantial heritability. There is no indication that the heritability estimate reported here is confounded by assortative mating. This study shows that the strong heritability is not limited to the clinical autism spectrum, but also accounts for variance in autistic traits in the general population. Singletons do not differ from twins in endorsement of autistic traits. Genetic studies may be facilitated by measuring autistic traits on a continuous scale like the AQ. Such studies can elucidate whether the genes associated with the clinical spectrum are also associated with normal variation in autistic traits.

Correspondence: Rosa A. Hoekstra, MSc, Department of Biological Psychology, Vrije University, Van der Boechorststraat 1, Amsterdam 1081 BT, the Netherlands (ra.hoekstra@psy.vu.nl).

Accepted for Publication: November 15, 2006.

Author Contributions:Study concept and design: Hoekstra, Bartels, and Boomsma. Acquisition of data: Hoekstra and Verweij. Analysis and interpretation of data: Hoekstra, Bartels, Verweij, and Boomsma. Drafting of the manuscript: Hoekstra, Bartels, Verweij, and Boomsma. Critical revision of the manuscript for important intellectual content: Hoekstra, Bartels, and Boomsma. Statistical analysis: Hoekstra, Bartels, Verweij, and Boomsma. Obtained funding: Boomsma.

Financial Disclosure: None reported.

Funding/Support: This study was supported by grants NWO 575-25-006 and NWO/SPI 56-464-14192, and Dr Bartels is supported by grant NWO VENI 451-04-034 from the Netherlands Organization for Scientific Research.

Acknowledgment: We are very grateful to Simon Baron-Cohen, PhD, for his valuable feedback.

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.  Washington, DC American Psychiatric Association2000;
Rutter  M Genetic studies of autism: from the 1970s into the millennium. J Abnorm Child Psychol 2000;283- 14
PubMed Link to Article
Folstein  SRutter  M Genetic influences and infantile autism. Nature 1977;265726- 728
PubMed Link to Article
Bailey  ALe Couteur  AGottesman  I  et al.  Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;2563- 77
PubMed Link to Article
Le Couteur  ABailey  AGoode  S  et al.  A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry 1996;37785- 801
PubMed Link to Article
Bolton  PMacdonald  HPickles  A  et al.  A case-control family history study of autism. J Child Psychol Psychiatry 1994;35877- 900
PubMed Link to Article
Piven  JPalmer  PJacobi  DChildress  DArndt  S Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. Am J Psychiatry 1997;154185- 190
PubMed
Bailey  APalferman  SHeavey  LLe Couteur  A Autism: the phenotype in relatives. J Autism Dev Disord 1998;28369- 392
PubMed Link to Article
Constantino  JNTodd  RD Autistic traits in the general population: a twin study. Arch Gen Psychiatry 2003;60524- 530
PubMed Link to Article
Baron-Cohen  SWheelwright  SSkinner  RMartin  CE The Autism-Spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord 2001;315- 17
PubMed Link to Article
Spiker  DLotspeich  LJDimiceli  SMyers  RMRisch  N Behavioral phenotypic variation in autism multiplex families: evidence for a continuous severity gradient. Am J Med Genet 2002;114129- 136
PubMed Link to Article
Constantino  JNLajonchere  CLutz  M  et al.  Autistic social impairment in the siblings of children with pervasive developmental disorders. Am J Psychiatry 2006;163294- 296
PubMed Link to Article
Bishop  DVMMaybery  MMaley  AWong  DHill  WHallmayer  J Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism-Spectrum Quotient. J Child Psychol Psychiatry 2004;451431- 1436
PubMed Link to Article
Constantino  JNTodd  RD Intergenerational transmission of subthreshold autistic traits in the general population. Biol Psychiatry 2005;57655- 660
PubMed Link to Article
Constantino  JNTodd  RD Genetic structure of reciprocal social behavior. Am J Psychiatry 2000;1572043- 2045
PubMed Link to Article
Ronald  AHappe  FPlomin  R The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism. Dev Sci 2005;8444- 458
PubMed Link to Article
Ronald  AHappe  FBolton  P  et al.  Genetic heterogeneity between the three components of the autism spectrum: a twin study. J Am Acad Child Adolesc Psychiatry 2006;45691- 699
PubMed Link to Article
Achenbach  TMMcConaughy  SHHowell  CT Child/adolescent behavioral and emotional problems: implications of cross-informant correlations for situational specificity. Psychol Bull 1987;101213- 232
PubMed Link to Article
Verhulst  FCvan der Ende  J Agreement between parents' reports and adolescents' self-reports of problem behavior. J Child Psychol Psychiatry 1992;331011- 1023
PubMed Link to Article
Baron-Cohen  S The hyper-systemizing, assortative mating theory of autism. Prog Neuropsychopharmacol Biol Psychiatry 2006;30865- 872
PubMed Link to Article
Phillips  KFulker  DWCarey  GNagoshi  CT Direct marital assortment for cognitive and personality variables. Behav Genet 1988;18347- 356
PubMed Link to Article
Mascie-Taylor  CGVandenberg  SG Assortative mating for IQ and personality due to propinquity and personal preference. Behav Genet 1988;18339- 345
PubMed Link to Article
Watson  DKlohnen  ECCasillas  ASimms  ENHaig  JBerry  DS Match makers and deal breakers: analyses of assortative mating in newlywed couples. J Pers 2004;721029- 1068
PubMed Link to Article
Boomsma  DIOrlebeke  JFVan Baal  GCM The Dutch Twin Register: growth data on weight and height. Behav Genet 1992;22247- 251
PubMed Link to Article
Boomsma  DIVink  JMVan Beijsterveldt  CEM  et al.  Netherlands Twin Register: a focus on longitudinal research. Twin Res 2002;5401- 406
PubMed Link to Article
Rietveld  MJHDer Valk  JCBongers  ILStroet  TMSlagboom  PEBoomsma  DI Zygosity diagnosis in young twins by parental report. Twin Res 2000;3134- 141
PubMed Link to Article
Neale  MCBoker  SMXie  GMaes  HH Mx: Statistical Modeling, Revised. 6th ed. Richmond Virginia Commonwealth University2005;
Wakabayashi  ABaron-Cohen  SWheelwright  STojo  Y The Autism-Spectrum Quotient (AQ) in Japan: a cross-cultural comparison. J Autism Dev Disord 2006;36263- 270
PubMed Link to Article
Fombonne  E Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 2003;33365- 382
PubMed Link to Article
Greenberg  DAHodge  SESowinski  JNicoll  D Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001;691062- 1067
PubMed Link to Article
Betancur  CLeboyer  MGillberg  C Increased rate of twins among affected sibling pairs with autism. Am J Hum Genet 2002;701381- 1383
PubMed Link to Article
Hallmayer  JGlasson  EJBower  C  et al.  On the twin risk in autism. Am J Hum Genet 2002;71941- 946
PubMed Link to Article
Croen  LAGrether  JKSelvin  S Descriptive epidemiology of autism in a California population: who is at risk? J Autism Dev Disord 2002;32217- 224
PubMed Link to Article
Hultman  CMSparen  PCnattingius  S Perinatal risk factors for infantile autism. Epidemiology 2002;13417- 423
PubMed Link to Article
Szatmari  PJones  MBZwaigenbaum  LMacLean  JE Genetics of autism: overview and new directions. J Autism Dev Disord 1998;28351- 368
PubMed Link to Article
Posthuma  DBoomsma  DI A note on the statistical power in extended twin designs. Behav Genet 2000;30147- 158
PubMed Link to Article
Posserud  MBLundervold  AJGillberg  C Autistic features in a total population of 7-9-year-old children assessed by the ASSQ (Autism Spectrum Screening Questionnaire). J Child Psychol Psychiatry 2006;47167- 175
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Univariate path diagram representing the contribution of additive genetic (A), shared environmental (C), and nonshared environmental (E) influences to the trait under investigation (Autism-Spectrum Quotient scores). The factor loadings of these influences are represented by a, c, and e. The correlation of the additive genetic factors is 1.0 in monozygotic twins and, on average, 0.5 in dizygotic twins and between twins and siblings. The correlation of the shared environmental effects is 1.0 between twins and between twins and siblings. E represents effects unique to a family member and are thus uncorrelated.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Distribution of Autism-Spectrum Quotient (AQ) scores in twins and their siblings.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Sample Size and AQ Score in Twins, Their Siblings, and in Spouses
Table Graphic Jump LocationTable 2. Twin and Twin-Sibling Correlations
Table Graphic Jump LocationTable 3. Model Fit Statistics and Parameter Estimates for the Best-Fitting Model

References

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.  Washington, DC American Psychiatric Association2000;
Rutter  M Genetic studies of autism: from the 1970s into the millennium. J Abnorm Child Psychol 2000;283- 14
PubMed Link to Article
Folstein  SRutter  M Genetic influences and infantile autism. Nature 1977;265726- 728
PubMed Link to Article
Bailey  ALe Couteur  AGottesman  I  et al.  Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;2563- 77
PubMed Link to Article
Le Couteur  ABailey  AGoode  S  et al.  A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry 1996;37785- 801
PubMed Link to Article
Bolton  PMacdonald  HPickles  A  et al.  A case-control family history study of autism. J Child Psychol Psychiatry 1994;35877- 900
PubMed Link to Article
Piven  JPalmer  PJacobi  DChildress  DArndt  S Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. Am J Psychiatry 1997;154185- 190
PubMed
Bailey  APalferman  SHeavey  LLe Couteur  A Autism: the phenotype in relatives. J Autism Dev Disord 1998;28369- 392
PubMed Link to Article
Constantino  JNTodd  RD Autistic traits in the general population: a twin study. Arch Gen Psychiatry 2003;60524- 530
PubMed Link to Article
Baron-Cohen  SWheelwright  SSkinner  RMartin  CE The Autism-Spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord 2001;315- 17
PubMed Link to Article
Spiker  DLotspeich  LJDimiceli  SMyers  RMRisch  N Behavioral phenotypic variation in autism multiplex families: evidence for a continuous severity gradient. Am J Med Genet 2002;114129- 136
PubMed Link to Article
Constantino  JNLajonchere  CLutz  M  et al.  Autistic social impairment in the siblings of children with pervasive developmental disorders. Am J Psychiatry 2006;163294- 296
PubMed Link to Article
Bishop  DVMMaybery  MMaley  AWong  DHill  WHallmayer  J Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism-Spectrum Quotient. J Child Psychol Psychiatry 2004;451431- 1436
PubMed Link to Article
Constantino  JNTodd  RD Intergenerational transmission of subthreshold autistic traits in the general population. Biol Psychiatry 2005;57655- 660
PubMed Link to Article
Constantino  JNTodd  RD Genetic structure of reciprocal social behavior. Am J Psychiatry 2000;1572043- 2045
PubMed Link to Article
Ronald  AHappe  FPlomin  R The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism. Dev Sci 2005;8444- 458
PubMed Link to Article
Ronald  AHappe  FBolton  P  et al.  Genetic heterogeneity between the three components of the autism spectrum: a twin study. J Am Acad Child Adolesc Psychiatry 2006;45691- 699
PubMed Link to Article
Achenbach  TMMcConaughy  SHHowell  CT Child/adolescent behavioral and emotional problems: implications of cross-informant correlations for situational specificity. Psychol Bull 1987;101213- 232
PubMed Link to Article
Verhulst  FCvan der Ende  J Agreement between parents' reports and adolescents' self-reports of problem behavior. J Child Psychol Psychiatry 1992;331011- 1023
PubMed Link to Article
Baron-Cohen  S The hyper-systemizing, assortative mating theory of autism. Prog Neuropsychopharmacol Biol Psychiatry 2006;30865- 872
PubMed Link to Article
Phillips  KFulker  DWCarey  GNagoshi  CT Direct marital assortment for cognitive and personality variables. Behav Genet 1988;18347- 356
PubMed Link to Article
Mascie-Taylor  CGVandenberg  SG Assortative mating for IQ and personality due to propinquity and personal preference. Behav Genet 1988;18339- 345
PubMed Link to Article
Watson  DKlohnen  ECCasillas  ASimms  ENHaig  JBerry  DS Match makers and deal breakers: analyses of assortative mating in newlywed couples. J Pers 2004;721029- 1068
PubMed Link to Article
Boomsma  DIOrlebeke  JFVan Baal  GCM The Dutch Twin Register: growth data on weight and height. Behav Genet 1992;22247- 251
PubMed Link to Article
Boomsma  DIVink  JMVan Beijsterveldt  CEM  et al.  Netherlands Twin Register: a focus on longitudinal research. Twin Res 2002;5401- 406
PubMed Link to Article
Rietveld  MJHDer Valk  JCBongers  ILStroet  TMSlagboom  PEBoomsma  DI Zygosity diagnosis in young twins by parental report. Twin Res 2000;3134- 141
PubMed Link to Article
Neale  MCBoker  SMXie  GMaes  HH Mx: Statistical Modeling, Revised. 6th ed. Richmond Virginia Commonwealth University2005;
Wakabayashi  ABaron-Cohen  SWheelwright  STojo  Y The Autism-Spectrum Quotient (AQ) in Japan: a cross-cultural comparison. J Autism Dev Disord 2006;36263- 270
PubMed Link to Article
Fombonne  E Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 2003;33365- 382
PubMed Link to Article
Greenberg  DAHodge  SESowinski  JNicoll  D Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001;691062- 1067
PubMed Link to Article
Betancur  CLeboyer  MGillberg  C Increased rate of twins among affected sibling pairs with autism. Am J Hum Genet 2002;701381- 1383
PubMed Link to Article
Hallmayer  JGlasson  EJBower  C  et al.  On the twin risk in autism. Am J Hum Genet 2002;71941- 946
PubMed Link to Article
Croen  LAGrether  JKSelvin  S Descriptive epidemiology of autism in a California population: who is at risk? J Autism Dev Disord 2002;32217- 224
PubMed Link to Article
Hultman  CMSparen  PCnattingius  S Perinatal risk factors for infantile autism. Epidemiology 2002;13417- 423
PubMed Link to Article
Szatmari  PJones  MBZwaigenbaum  LMacLean  JE Genetics of autism: overview and new directions. J Autism Dev Disord 1998;28351- 368
PubMed Link to Article
Posthuma  DBoomsma  DI A note on the statistical power in extended twin designs. Behav Genet 2000;30147- 158
PubMed Link to Article
Posserud  MBLundervold  AJGillberg  C Autistic features in a total population of 7-9-year-old children assessed by the ASSQ (Autism Spectrum Screening Questionnaire). J Child Psychol Psychiatry 2006;47167- 175
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 97

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
The Roots of Autism and ADHD Twin Study in Sweden (RATSS). Twin Res Hum Genet 2014;17(3):164-76.
The familial risk of autism. JAMA 2014;311(17):1770-7.