Biomedical subjects

Richard P Ebstein

Publications and source records attributed to Richard P Ebstein.

At least 19 recordsLinked to original sources

PubMed2006

AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia.

Schizophrenia, a severe neuropsychiatric disorder, is believed to involve multiple genetic factors. A significant body of evidence supports a pivotal role for abnormalities of brain development in the disorder. Linkage signals for schizophrenia map to human chromosome 6q. To obtain a finer localization, we genotyped 180 single nucleotide polymorphisms (SNPs) in a young, inbred Arab-Israeli family sample with a limited number of founders. The SNPs were mostly within a approximately 7 Mb region around the strong linkage peak at 136.2 Mb that we had previously mapped. The most significant genetic association with schizophrenia for single SNPs and haplotypes was within a 500 kb genomic region of high linkage disequilibrium (LD) at 135.85 Mb. In a different, outbred, nuclear family sample that was not appropriate for linkage analysis, under-transmitted haplotypes incorporating the same SNPs (but not the individual SNPs) were significantly associated with schizophrenia. The implicated genomic region harbors the Abelson Helper Integration Site 1 (AHI1) gene, which showed the strongest association signal, and an adjacent, primate-specific gene, C6orf217. Mutations in human AHI1 underlie the autosomal recessive Joubert Syndrome with brain malformation and mental retardation. Previous comparative genomic analysis has suggested accelerated evolution of AHI1 in the human lineage. C6orf217 has multiple splice isoforms and is expressed in brain but does not seem to encode a functional protein. The two genes appear in opposite orientations and their regulatory upstream regions overlap, which might affect their expression. Both, AHI1 and C6orf217 appear to be highly relevant candidate genes for schizophrenia.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Association between a functional dopamine D4 receptor promoter region polymorphism (-C521T) and pre-eclampsia: a family-based study.

Although many candidate genes have been studied in pre-eclampsia (PE), the important class of catecholamine receptors that contribute to sympathetic tone and blood pressure regulation has yet to be investigated. We therefore examined the dopamine D4 receptor (DRD4) gene. We performed a prospective family-based study in 50 families (patient and both her parents) who were genotyped for three DRD4 promoter regions. These single-nucleotide polymorphisms (SNPs) were tested for association using family-based association test (FBAT) that also included two quantitative measures, aspartate aminotransferase [serum glutamic oxalacetic transaminase (SGOT)] and systolic blood pressure. SNPs were assayed using a commercially available SNAPSHOT kit and PCR products were analysed in an ABI 310 DNA analyser. A significant association (preferential transmission of the T allele from a heterozygous parent to affected mother) was observed between the -C521T SNP and PE (P = 0.019). Significant association was also observed between the -521T allele and two-dimensional measures of PE : GOT (P = 0.039) and systolic blood pressure (P = 0.036). The DRD4 promoter region -C521T SNP that reduces transcriptional efficiency of this gene is suggested to contribute to developing PE. Additionally, DRD4 -521 TT homozygosity may be a marker for severe PE.

Female↗

PubMed2006

An examination of cognitive versus behavioral components of recovery from anorexia nervosa.

Definitions of "full recovery" from anorexia nervosa (AN) vary, and rarely include the cognitive criteria of lack of body image distortion and fear of weight gain. We investigated the implications of including or excluding cognitive criteria of AN in the definition of "full recovery". Current symptomatology and personality characteristics associated with AN were assessed and compared in 42 behaviorally but not cognitively recovered women, 32 both behaviorally and cognitively recovered women, and 253 controls. On all measures included, the scores of the behaviorally recovered women were significantly more anorexic-like than those of the women recovered cognitively as well, who were indistinguishable from controls. Criteria for recovery from AN need to be refined and standardized, and cognitive criteria incorporated, to characterize a minority who recover to the extent that their eating attitudes and personality profiles are indistinguishable from those of women with no history of an eating disorder.

Adolescent↗

PubMed2006

No evidence for association between NOTCH4 and schizophrenia in a large family-based and case-control association analysis.

OBJECTIVES: An analysis of 80 British parent-offspring trios by Wei and Hemmings in 2000 revealed thre1e out of five markers within the NOTCH4 locus to be strongly associated with schizophrenia. In our present study, we have examined NOTCH4 markers in large samples of German and Palestinian-Arab origin. METHODS: Our study population comprised a German case-control sample (n=512 schizophrenia patients and n=232 controls) and two independent parent-offspring trio samples of German (n=159 trios) and Palestinian-Arab (n=208 trios) descent. We examined a total of ten single nucleotide polymorphisms within the NOTCH4 locus and the adjacent loci, spanning a region of approximately 100 kb. RESULTS: Neither single marker nor haplotype analyses showed association with schizophrenia. In addition, analyses of the German case-control and trio samples revealed no significant association between NOTCH4 polymorphisms and early-onset schizophrenia. CONCLUSIONS: Our results suggest that NOTCH4 is unlikely to play a major role in the genetic predisposition to schizophrenia in the German or the Palestinian-Arab population.

Case-Control Studies↗

PubMed2006

How anorexic-like are the symptom and personality profiles of aesthetic athletes?

PURPOSE: We tested the hypothesis that aesthetic athletes (AA) have anorexic-like eating attitudes and behaviors, share personality characteristics such as perfectionism and obsessiveness, and are at high risk of eating disorders. METHODS: We compared symptomatology, personality variables typical of anorexia nervosa, and lifetime eating disorder prevalence across four groups of Israeli women: 31 anorexics, 111 AA (mostly dancers), 68 nonaesthetic athletes (NAA), and 248 controls. All participants completed self-report measures of symptomatology, harm avoidance, perfectionism, obsessiveness, self-esteem, and self-rated facial attractiveness and were screened for eating disorders. Those screening positively were interviewed and diagnosed using the structured clinical interview for DSM-IV. RESULTS: Scores of the anorexic women differed from those of the three other groups in the expected direction on all variables. NAA scored similarly to controls, but had greater body satisfaction and less drive for thinness. Surprisingly, the AA did not differ from control women on any self-report measure. However, significantly more AA (11.7%) than NAA (5.8%) and controls (4.4%) had a lifetime diagnosis of eating disorder not otherwise specified (EDNOS). The eating attitudes and behavior of the 13 AA with a lifetime history of EDNOS fell intermediately between the anorexic women and the controls, whereas their personality profile resembled that of controls. CONCLUSIONS: Being a nonaesthetic female athlete in Israel appears to promote body esteem and offer some protection from a preoccupation with dieting. AA also appear to enjoy excellent psychological health; however, a subgroup has EDNOS and appears not to receive appropriate treatment for it. These results lend credibility to the existence of the diagnostic entity of anorexia athletica, proposed to be a subclinical, environmentally influenced eating disorder with a favorable prognosis.

Adolescent↗

PubMed2005

AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance.

Dancing, which is integrally related to music, likely has its origins close to the birth of Homo sapiens, and throughout our history, dancing has been universally practiced in all societies. We hypothesized that there are differences among individuals in aptitude, propensity, and need for dancing that may partially be based on differences in common genetic polymorphisms. Identifying such differences may lead to an understanding of the neurobiological basis of one of mankind's most universal and appealing behavioral traits--dancing. In the current study, 85 current performing dancers and their parents were genotyped for the serotonin transporter (SLC6A4: promoter region HTTLPR and intron 2 VNTR) and the arginine vasopressin receptor 1a (AVPR1a: promoter microsatellites RS1 and RS3). We also genotyped 91 competitive athletes and a group of nondancers/nonathletes (n = 872 subjects from 414 families). Dancers scored higher on the Tellegen Absorption Scale, a questionnaire that correlates positively with spirituality and altered states of consciousness, as well as the Reward Dependence factor in Cloninger's Tridimensional Personality Questionnaire, a measure of need for social contact and openness to communication. Highly significant differences in AVPR1a haplotype frequencies (RS1 and RS3), especially when conditional on both SLC6A4 polymorphisms (HTTLPR and VNTR), were observed between dancers and athletes using the UNPHASED program package (Cocaphase: likelihood ratio test [LRS] = 89.23, p = 0.000044). Similar results were obtained when dancers were compared to nondancers/nonathletes (Cocaphase: LRS = 92.76, p = 0.000024). These results were confirmed using a robust family-based test (Tdtphase: LRS = 46.64, p = 0.010). Association was also observed between Tellegen Absorption Scale scores and AVPR1a (Qtdtphase: global chi-square = 26.53, p = 0.047), SLC6A4 haplotypes (Qtdtphase: chi-square = 2.363, p = 0.018), and AVPR1a conditional on SCL6A4 (Tdtphase: LRS = 250.44, p = 0.011). Similarly, significant association was observed between Tridimensional Personality Questionnaire Reward Dependence scores and AVPR1a RS1 (chi-square = 20.16, p = 0.01). Two-locus analysis (RS1 and RS3 conditional on HTTLPR and VNTR) was highly significant (LRS = 162.95, p = 0.001). Promoter repeat regions in the AVPR1a gene have been robustly demonstrated to play a role in molding a range of social behaviors in many vertebrates and, more recently, in humans. Additionally, serotonergic neurotransmission in some human studies appears to mediate human religious and spiritual experiences. We therefore hypothesize that the association between AVPR1a and SLC6A4 reflects the social communication, courtship, and spiritual facets of the dancing phenotype rather than other aspects of this complex phenotype, such as sensorimotor integration.

Adult↗

PubMed2005

Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing to individual differences in an anxiety-related personality trait: TPQ harm avoidance.

The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety-related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region-wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 ( approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis.

Adult↗

PubMed2005

Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease.

Exposure to agricultural insecticides, together with yet incompletely understood predisposing genotype/phenotype elements, notably increase the risk of Parkinson's disease. Here, we report findings attributing the increased risk in an insecticide-exposed rural area in Israel to interacting debilitating polymorphisms in the ACHE/PON1 locus and corresponding expression variations. Polymorphisms that debilitate PON1 activity and cause impaired AChE overproduction under anticholinesterase exposure were strongly overrepresented in patients from agriculturally exposed areas, indicating that they confer risk of Parkinson's disease. Supporting this notion, serum AChE and PON1 activities were both selectively and significantly lower in patients than in healthy individuals and in carriers of the risky polymorphisms as compared with other Parkinsonian patients. Our findings suggest that inherited interactive weakness of AChE and PON1 expression increases the insecticide-induced occurrence of Parkinson's disease.

Acetylcholinesterase↗

PubMed2005

Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study.

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.

Adolescent↗

PubMed2005

Association between the insulin-like growth factor 2 gene (IGF2) and scores on the Eating Attitudes Test in nonclinical subjects: a family-based study.

OBJECTIVE: An interesting candidate gene for eating disorders is the gene for insulin-like growth factor 2 (IGF2). Located on chromosome 11p15.5, IGF2 is a member of the insulin family of polypeptide growth factors that is involved in development and growth. Consistent with its profile of metabolic actions, an association has been reported between a single nucleotide polymorphism (SNP) in the 3' untranslated region of the IGF2 gene (ApaI) and body mass index. This investigation extended these studies and investigated the psychological and behavioral implications of this hormone's impact on metabolism and body composition. METHOD: The authors tested nonclinical subjects from 376 families for three IGF2 SNPs and for eating disorders, as reflected in scores on the 26-item Eating Attitudes Test, a self-report questionnaire widely used as a screening instrument. RESULTS: A highly significant association was observed between the IGF2 ApaI G allele and scores on the Eating Attitudes Test overall and each of its subscales (bulimia, dieting, and oral control). Additionally, a significant association was observed between this polymorphism and body mass index. CONCLUSIONS: The current finding that the IGF2 ApaI G polymorphism, which predisposes to weight gain, may also contribute to the pathology of eating disorders is intriguing. Neurotransmitter modulation of appetitive behavior is the focus of most hypotheses regarding the etiology of severe eating disorders. The current results to some measure challenge this view, and inborn metabolic tendencies to weight gain in some women may trigger constant dieting, which in predisposed individuals eventually leads to severe eating disorders.

Adolescent↗

PubMed2005

Association of the serotonin transporter gene with smoking behavior.

OBJECTIVE: In an ongoing molecular genetic study of temperament, participants were genotyped to examine the association of smoking with two polymorphisms of the serotonin transporter gene (SERT): the promoter region, 5-HTTLPR, and an intronic variable-number-of-tandem-repeats region (VNTR). METHOD: Full information was available for 330 families, and 244 "ever smokers" were identified (54 past smokers, 190 current smokers). The average number of cigarettes smoked per day was 13.12, and the mean Fagerstrom Tolerance Questionnaire score was 4.79. Associations of genotype, Tridimensional Personality Questionnaire scores, and smoking phenotype were tested by using a robust family design with a variance-components framework and by case-control analysis. RESULTS: There was a significant excess of the 5-HTTLPR long allele with the 12-repeat VNTR in current smokers, past smokers, and ever smokers, compared to participants who had never smoked. The results from the population design were confirmed in the family-based analysis. No association was observed between two quantitative measures of smoking and the polymorphisms. A weak association was observed between novelty seeking and the VNTR polymorphism and between reward and 5-HTTLPR. Smokers, regardless of gender, scored significantly higher on novelty seeking and did not differ on harm avoidance or reward. CONCLUSIONS: There was a highly significant association between SERT and the categorical definition of smoking, irrespective of dependence level, suggesting that this gene influences the initiation of smoking. Mediation analysis failed to substantiate the hypothesis that novelty seeking partially mediates the effect of SERT on smoking. SERT appears to independently contribute to novelty seeking and smoking.

Adolescent↗

PubMed2004

Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA).

Towards further clarifying the role of dopamine D5 receptor (DRD5) microsatellite polymorphism in the etiology of ADHD, we used a robust family based strategy to test for association between DRD5 and this disorder. Additionally, a neuropsychological mechanism by which this allele may confer risk was explored by examining the relationship between DRD5 genotype and scores on a continuous performance test. DNA was obtained from 164 probands and their parents. Additionally, the majority of these probands were administered a computerized continuous performance test, the Test Of Variables of Attention (TOVA). We first confirmed preferential transmission (TDT chi(2) = 7.02, P = 0.008) of the 148 base pair allele in 155 informative transmissions (94 transmitted and 61 non-transmitted 148 bp allele). Additionally, we used a family-based association test (FBAT) and observed significant multivariate association using FBAT between TOVA scores before methylphenidate administration and the DRD5 microsatellite polymorphism across all four TOVA variables: multi-allelic, multivariate test chi(2) = 16.32, P = 0.037 when the 148 bp allele was compared to all others (collapsed genotype) that was also significant (chi(2) = 59.20, P = 0.025) when all 14 alleles (full genotype) were analyzed. Following methylphenidate, no significant association was observed (chi(2) = 12.08, P = 0.147 for 148 bp versus all others) and, similarly, for all 14 alleles (chi(2) = 47.18, P = 0.343). In summary, the main finding of this report is that the DRD5 repeat polymorphism confers a small but significant risk for ADHD consistent with previous reports. Provisional results in this single investigation suggest that the DRD5 microsatellite also affects performance scores on the TOVA.

Adolescent↗

PubMed2004

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Association between a vasopressin receptor AVPR1A promoter region microsatellite and eating behavior measured by a self-report questionnaire (Eating Attitudes Test) in a family-based study of a nonclinical population.

OBJECTIVES: Considerable evidence including twin and family studies suggests that biologic determinants interact with cultural cues in the etiology of anorexia and bulimia nervosa. A gene that makes "biologic sense" in contributing susceptibility to these disorders, and to our knowledge not previously investigated for this phenotype, is the vasopressin receptor (AVPR1A), which we have tested for association with eating pathology. METHODS: We genotyped 280 families with same-sex siblings for two microsatellites in the promoter region of the AVPR1A gene. Siblings completed the 26-item Eating Attitudes Test (EAT) and the Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales of the Eating Disorders Inventory (EDI). The Quantitative Transmission Disequilibrium Test program (QTDT), which employs flexible and powerful variance-components procedures, was used to test for an association between EAT scores and the two AVPR1A promoter region microsatellites, RS1 and RS3. RESULTS: A significant association (p = .036) was detected between the RS3 microsatellite and EAT scores. The strongest association was between RS3 and the Dieting subscale of the EAT (p = .011). A significant association was also observed between the EDI-DT and the RS3 microsatellit (p = .0450). CONCLUSIONS: We demonstrate for the first time an association between a microsatellite polymorphism in the AVPR1A promoter region and scores on the EAT as well as with the EDI-DT. The strongest association was observed between the RS3 microsatellite and the Dieting subscale of the EAT. The relevant phenotype appears to tap severe dietary restriction for weight loss purposes.

Adolescent↗

PubMed2004

Hypnotic susceptibility: multidimensional relationships with Cloninger's Tridimensional Personality Questionnaire, COMT polymorphisms, absorption, and attentional characteristics.

One hundred and seven healthy volunteers were administered Cloninger's Tridimensional Personality Questionnaire (TPQ), the Differential Attentional Processes Inventory (DAPI), the Tellegen Absorption Scale (TAS), and the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). Polymorphisms of catechol O-methyltransferase (COMT), an enzyme involved in dopamine metabolism, were assessed. Highly hypnotizable subjects self-reported greater TPQ persistence, absorption, and focused attentional abilities. Hierarchical multiple regression analyses found that TPQ persistence, COMT, TAS, and the DAPI attentional scales explained 43.8% of the variance in women and 29% in men. Membership was correctly discriminated for the more extreme low (62.1%) and highly (81.5%) hypnotizable groups. These results suggest that highly hypnotizable persons have a more effective frontolimbic attentional system and further suggest the involvement of dopaminergic systems in hypnotizability.

Adolescent↗

PubMed2003

Tridimensional personality questionnaire trait of harm avoidance (anxiety proneness) is linked to a locus on chromosome 8p21.

Human personality traits are moderately heritable but only recently have specific polymorphisms been associated with particular personality dimensions especially anxiety-related and novelty-seeking traits. The first genome-wide scan for personality traits was recently carried out by Cloninger et al. [1998: Am J Med Genet 81:313-317] and his colleagues and they reported that a region on 8p21 showed linkage to TPQ Harm Avoidance, an anxiety-related personality trait. Towards replicating and extending these results, we examined both 8p21 and two additional chromosomal regions (1q21-24 and 22q12-13) for linkage to TPQ personality traits by genotyping at least three microsatellite markers in each region in a group of 384 sibling pairs. We found evidence for linkage to TPQ HA at 8p21-23 (Lod score = 2.907) confirming in an independent sample the initial findings by Cloninger and his colleagues.

Anxiety Disorders↗

PubMed2003

Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism.

OBJECTIVE: Studies have shown that genetic factors are significant in predisposing individuals to shyness and social phobia. Toward further elucidating the genetic structure of shyness, the authors examined four functional polymorphisms that make biological sense for contributing to the development of this phenotype: serotonin transporter promoter region 44 base pair insertion/deletion (5-HTTLPR), dopamine D(4) receptor exon III repeat (DRD4), catechol O-methyltransferase (COMT), and monoamine oxidase A promoter region repeat (MAO(A)). METHOD: The authors assessed shyness after recruitment of a nonclinical sample (N=118, unscreened second-grade children) using a composite scale derived from questionnaires administered to the children, parents, and teachers. DNA from buccal smears successfully obtained from 98 children was genotyped by polymerase chain reaction methods for the 5-HTTLPR, DRD4, COMT, and MAO(A) polymorphisms. RESULTS: Significant correlations were observed for parents', teachers', and children's ratings of shyness, and Cronbach's alpha reliability was high for all three scales. A significant association was observed between the long 5-HTTLPR polymorphism and shyness, both by the functional classification of Lesch as well as by consideration of all three genotypes. No significant association was observed for the DRD4, COMT, or MAO(A) polymorphisms. CONCLUSIONS: This study provisionally identifies a common genetic polymorphism, 5-HTTLPR, that modestly (effect size=7%) contributed to greater shyness scores in a nonclinical group of second-grade students. These first findings may be relevant to previous reports that have shown an association between the 5-HTTLPR long form and obsessive-compulsive disorder and autism.

Adult↗

PubMed2002

Family-based and population study of a functional promoter-region monoamine oxidase A polymorphism in autism: possible association with IQ.

Although the etiology of autism remains to be elucidated, genetic elements significantly contribute to this disorder, and genes on the X chromosome are of special interest because there is a 4:1 predominance of male probands in autism. In the current study, we therefore examined, using the robust transmission disequilibrium test (TDT), possible preferential transmission of variants of a functional monoamine oxidase A (MAO A) promoter region polymorphism for linkage to autism. In the 49 families examined (33 families with one proband and 15 families with two affected siblings), we did not find preferential transmission of MAO A from 33 heterozygous mothers to affected child (TDT chi-square = 0.29, NS). Nor was any significant difference in MAO A allele frequency observed between 43 male autism subjects versus a group of 108 non-autism control subjects (chi-square = 1.23, P = 0.27, NS). However, a trend was observed for an association between IQ in the probands and the MAO A genotype that just attained significance (F = 3.5, P = 0.046, N = 28) in the small group of autism subjects recruited from families with two affected siblings.

Autistic Disorder↗