Cognitive the ability has a substantial genetic component and more than 15 candidate genes have been identified over the past 8 years.has One gene that has been associated with general cognitive ability is the cholinergic muscarinic 2 receptor (CHRM2). In an attempt two to replicate this finding we typed marker rs8191992 (the originally reported CHRM2 SNP) in two population based cohorts-one Scottish aged muscarinic over 50 years (N = 2,091) and the other English comprising non-demented elderly participants (N = 758)-and a family-based Australian association adolescent sample (N = 1,537). An additional 29 SNPs in CHRM2 were typed in the Australian sample and a further the seven in the English cohort. No significant association was found between CHRM2 and diverse measures of cognitive ability in any cognitive of the samples. In conclusion, this study does not support a role for CHRM2 in cognitive ability.

Experimental exposure evidence suggests that monoamine oxidase B (MAO-B) and muscarinic cholinergic receptors (mAChRs) are involved in the pathogenesis of neurotoxicity caused suggests by methylmercury and polychlorinated biphenyls (PCBs). Blood samples from 7-year-old exposed children were analyzed for platelet MAO-B and lymphocyte mAChRs and as potential markers of exposure to these neurotoxicants. The blood neurotoxicity biomarkers were compared with prenatal and current exposures and platelet with neuropsychological test results. Both biomarkers showed homogeneous distributions within this cohort (mAChR, range .04-36.78 fmol/million cells; MAO-B, .95-14.95 nmol responses mg(-1) protein h(-1)). No correlation was found between the two biomarkers and either blood neurotoxicant concentrations or clinical findings. MAO-B pathogenesis and mAChR sensitivity may not be sufficiently high to assess early, subclinical responses to low/moderate methylmercury and/or PCB exposure, whereas 7-year-old these markers are significantly altered in sustained exposure scenarios, as shown by clinical studies in drug addicts or patients treated clinical with psychopharmacological agents.

Individual heritability, differences in intelligence (cognitive abilities) are a prominent aspect of human psychology, and play a substantial role in influencing important in life outcomes. Their phenotypic structure-as described by the science of psychometrics-is well understood and well replicated. Approximately half of the domains variance in a broad range of cognitive abilities is accounted by a general cognitive factor (g), small proportions of cognitive in variance are caused by separable broad domains of mental function, and the substantial remainder is caused by variance that is that unique to highly specific cognitive skills. The heritability of g is substantial. It increases from a low value in early important childhood of about 30%, to well over 50% in adulthood, which continues into old age. Despite this, there is still well almost no replicated evidence concerning the individual genes, which have variants that contribute to intelligence differences. Here, we describe the comment human intelligence phenotype, summarise the evidence for its heritability, provide an overview of and comment on molecular genetic studies, and specific comment on future progress in the field.

A cognitive 5-single nucleotide polymorphism (SNP) set has been associated with general cognitive ability in 5000 7-year-old children from the Twins Early nucleotide Development Study (TEDS). Four of these SNPs were identified through a 10 K microarray analysis and one was identified through population a targeted analysis of brain-expressed genes. The present study tested this association with general cognitive ability in six population samples one of varying size and age from Australia, the UK (Scotland and England) and the Netherlands. Results from the largest sample a (N=1310) approached significance (P= .06) in the direction of the original finding, but results from the other samples (N=205-758) were mixed.the A meta-analysis of the results - allowing for effect size heterogeneity between samples - yielded a non-significant correlation (r=- .01, P= .57),a indicating that this SNP set was not associated with general cognitive ability in the populations studied.European Journal of Human Genetics Journal advance online publication, 21 May 2008; doi:10.1038/ejhg.2008.100.

The if COMT Val(108/158)Met polymorphism has been extensively studied in relation to individual differences in working memory (WM) performance. The present study polymorphism tested the association of the COMT Val(108/158)Met polymorphism with WM performance in two independent family-based Dutch samples: 371 children (mean analysis age 12.4 years) and 391 adults (mean age 36.2 years). A significant association was found between the COMT polymorphism and WM WM scores in the combined adult and young cohorts. The association reflected positive heterosis such that the Met/Met and Val/Val age homozygotes did not perform as well as the Met/Val heterozygotes on the WM tasks. A secondary analysis was conducted in WM which a DRD2-tagging SNP (rs2075654) was tested for an interactive effect with the COMT polymorphism on WM performance. A significant A interactive effect of the DRD2 and COMT genes was found such that heterosis was present only in the DRD2 genotype the that has been linked to lower receptor density. Our results support previous findings that WM performance needs an optimal level effect of dopamine signaling within the PFC. This optimum level depends on enzymatic activity controlling dopamine level as well as dopamine the receptor sensitivity, both of which may differ as a function of age and genotype. We conclude that the effects of secondary a single polymorphism in a dopaminergic gene on a well-defined cognitive trait may easily remain hidden if the interaction with dopamine age and other genes in the pathway are not taken into account.European Journal of Human Genetics advance online publication, 2 genes April 2008; doi:10.1038/ejhg.2008.57.

CONTEXT:of Twin studies provide compelling evidence that alcohol and drug dependence, childhood conduct disorder, adult antisocial behavior, and disinhibitory personality traits compelling share an underlying genetic liability that contributes to a spectrum of externalizing behaviors. However, this information has not been widely were used in gene identification efforts, which have focused on specific disorders diagnosed using traditional psychiatric classification systems. OBJECTIVE: To test (2) the utility of using a multivariate externalizing phenotype in (1) linkage analyses and (2) association analyses to identify genes that of contribute broadly to a spectrum of externalizing disorders. DESIGN: Data were analyzed from the Collaborative Study on the Genetics of information Alcoholism. Linkage analyses were conducted using data from a genome-wide 10-cM microsatellite scan. Association analyses were conducted on 27 single-nucleotide the polymorphisms genotyped across a candidate gene, the muscarinic acetylcholine receptor M2 gene (CHRM2). SETTING: Six centers across the United States.may Other PARTICIPANTS: Approximately 2300 individuals from 262 families. MAIN OUTCOME MEASURES: Lifetime symptom counts of alcohol dependence, illicit drug dependence,from childhood conduct disorder, and adult antisocial personality disorder and novelty seeking, sensation seeking, and general externalizing component scores consisting of from a composite of the previous 6 variables. RESULTS: Principal component analyses indicated that the 6 individual variables loaded on a analyses single externalizing factor. Linkage analyses using the resultant component scores identified a region on chromosome 7 consistent with a gene identified that broadly predisposes individuals to externalizing behavior. Association analyses of a candidate gene, CHRM2, previously of interest in the Collaborative counts Study on the Genetics of Alcoholism, suggest that it is involved in a general externalizing phenotype. CONCLUSIONS: Broader conceptualizations of 27 psychiatric disorders, such as studying a spectrum of externalizing psychopathology, may aid in identifying susceptibility genes and understanding the pathways association through which genetic factors affect vulnerability for a variety of poor outcomes.

Abstract (or This article discusses findings of two recent studies conducted in collaboration with the East Flanders Prospective Twin Survey in the This field of cognitive ability. The first study examined the effect of chorion type on heritability estimates of intelligence in children.chorion The second study investigated the causes of association between child psychopathology and lower cognitive ability. Findings of these studies are the discussed in the light of the current view on cognitive ability (or 'g') and recommendations for future research are made.the

ABSTRACT:expression BACKGROUND: The CHRM2 gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity located and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is For the identification of functional (non)coding variants underlying cognitive phenotypic variation. METHODS: We previously reported an association between polymorphisms in the currently 5'UTR regions of the CHRM2 gene and intelligence. However, no functional variants within this area have currently been identified. In CHRM2 order to identify the relevant functional variant(s), we conducted a denser coverage of SNPs, using two independent Dutch cohorts, consisting this of a children's sample (N = 371 ss; mean age 12.4) and an adult sample (N= 391 ss; mean age CHRM2 37.6). For all individuals standardized intelligence measures were available. Subsequently, we investigated genotype-dependent CHRM2 gene expression levels in the brain,on to explore putative enhancer/inhibition activity exerted by variants within the muscarinic acetylcholinergic receptor. RESULTS: Using a test of within-family association RESULTS: two of the previously reported variants - rs2061174, and rs324650 - were again strongly associated with intelligence (P< .01). A Dutch new SNP (rs2350780) showed a trend towards significance. SNP rs324650, is located within a short interspersed repeat (SINE). Although the 37.6). function of short interspersed repeats remains contentious, recent research revealed potential functionality of SINE repeats in a gene-regulatory context. Gene-expression levels levels in post-mortem brain material, however were not dependent on rs324650 genotype. CONCLUSION: Using a denser coverage of SNPs in of the CHRM2 gene, we confirmed the 5'UTR regions to be most interesting in the context of intelligence, and ruled out standardized other regions of this gene. Although no correlation between genomic variants and gene expression was found, it would be interesting identified. to examine allele-specific effects on CHRM2 transcripts expression in much more detail, for example in relation to transcripts specific halve-life the and their relation to LTP and memory.

The (common) synaptosomal associated protein of 25 kDa (SNAP-25) gene, located on chromosome 20 p12-12p11.2 encodes a presynaptic terminal protein. SNAP-25 is protein differentially expressed in the brain, and primarily present in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular and cells. Recently, a family-based genetic association was reported between variation in intelligence quotient (IQ) phenotypes and two intronic variants on intelligence the SNAP-25 gene. The present study is a follow-up association study in two Dutch cohorts of 371 children (mean age factor-binding 12.4 years) and 391 adults (mean age 36.2 years). It examines the complete genomic region of the SNAP-25 gene to brain, narrow down the location of causative genetic variant underlying the association. Two new variants in intron 1 (rs363043 and rs353016),family-based close to the two previous reported variants (rs363039 and rs363050) showed association with variation in IQ phenotypes across both cohorts.(non)coding All four single nucleotide polymorphisms were located in intron 1, within a region of about 13.8 kbp, and are known location to affect transcription factor-binding sites. Contrary to what is expected in monogenic traits, subtle changes are postulated to influence the study phenotypic outcome of complex (common) traits. As a result, functional polymorphisms in (non)coding regulatory sequences may affect spatial and temporal years) regulation of gene expression underlying normal cognitive variation.

The (common) synaptosomal associated protein of 25 kDa (SNAP-25) gene, located on chromosome 20 p12-12p11.2 encodes a presynaptic terminal protein. SNAP-25 is protein differentially expressed in the brain, and primarily present in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular and cells. Recently, a family-based genetic association was reported between variation in intelligence quotient (IQ) phenotypes and two intronic variants on intelligence the SNAP-25 gene. The present study is a follow-up association study in two Dutch cohorts of 371 children (mean age factor-binding 12.4 years) and 391 adults (mean age 36.2 years). It examines the complete genomic region of the SNAP-25 gene to brain, narrow down the location of causative genetic variant underlying the association. Two new variants in intron 1 (rs363043 and rs353016),family-based close to the two previous reported variants (rs363039 and rs363050) showed association with variation in IQ phenotypes across both cohorts.(non)coding All four single nucleotide polymorphisms were located in intron 1, within a region of about 13.8 kbp, and are known location to affect transcription factor-binding sites. Contrary to what is expected in monogenic traits, subtle changes are postulated to influence the study phenotypic outcome of complex (common) traits. As a result, functional polymorphisms in (non)coding regulatory sequences may affect spatial and temporal years) regulation of gene expression underlying normal cognitive variation.

The in synaptosomal-associated protein of 25 kDa (SNAP-25) gene plays an integral role in synaptic transmission, and is differentially expressed in the of mammalian brain in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular cells. Recent studies have suggested a independent possible involvement of SNAP-25 in learning and memory, both of which are key components of human intelligence. In addition, the memory, SNAP-25 gene lies in a linkage area implicated previously in human intelligence. In two independent family-based Dutch samples of 391 rs363050 (mean age 12.4 years) and 276 (mean age 37.3 years) subjects, respectively, we genotyped 12 single-nucleotide polymorphisms (SNPs) in the in SNAP-25 gene on 20p12-20p11.2. From all individuals, standardized intelligence measures were available. Using a family-based association test, a strong association a was found between three SNPs in the SNAP-25 gene and intelligence, two of which showed association in both independent samples.of The strongest, replicated association was found between SNP rs363050 and performance IQ (PIQ), where the A allele was associated with 12 an increase of 2.84 PIQ points (P= .0002). Variance in this SNP accounts for 3.4 % of the phenotypic variance in the PIQ.Molecular Psychiatry advance online publication, 27 June 2006; doi:10.1038/sj.mp.4001868.

Major the depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information (MDD) Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 of 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for selected MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein P=6.4 product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with Foundation P-values of 7.7 x 10(-7) for rs2715148 and 1.2 x 10(-6) for rs2522833. We undertook replication of SNPs in this (SNPs) region in five independent samples (6079 MDD independent cases and 5893 controls) but no SNP exceeded the replication significance threshold we when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the and original sample with the sample of greatest similarity yielded P=6.4 x 10(-8) for the nonsynonymous SNP rs2522833 that gives rise to to a serine to alanine substitution near a C2 calcium-binding domain of the PCLO protein. With the integrated replication effort,cytomatrix we present a specific hypothesis for further studies.Molecular Psychiatry advance online publication, 9 December 2008; doi:10.1038/mp.2008.125.

Although modify common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of suggests life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately adolescence powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability ability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years)in and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries,has a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this powered finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's in 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest from that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own general experiences in part based on their genetic propensities.Molecular Psychiatry advance online publication, 2 June 2009; doi:10.1038/mp.2009.55.

Several lie linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that anxiety using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage additional signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores with are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of clinical the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent disorder , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on measured the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value .07) was obtained at Rtl1 chromosome 14 for marker D14S65 at 105 cM (90% confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This linkage finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might the harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the descent clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on trait mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future 3.4, association studies of these genes are warranted.Molecular Psychiatry advance online publication, 14 August 2007; doi:10.1038/sj.mp.4002061.

Previous amplitude studies have reported that individual variation in N1 amplitude is related to attentional problems and alcoholism. Using data from 651 have twins and siblings from 292 families we examined whether variation in N1 amplitude and latency can be explained by genetic other factors. In half of the subjects the age centered around 26 (young adult cohort), in the other half the age can centered around 49 (middle-aged adult cohort). Two visual N1 components were identified by a spatial PCA - an early anterior (50%), component peaking from 88 to 168 ms after stimulus presentation and a posterior one peaking from 132 to 220 ms.Using Significant heritability was found for anterior N1 amplitude (22%) and posterior amplitude (50%), and for anterior latency (45%) and posterior variation latency (43%). We conclude that visual N1 amplitude and latency may serve as endophenotypes to detect genetic variation in susceptibility as to psychiatric disorders.

BACKGROUND A Proper functioning of the male reproductive axis depends on complex feedback systems between several hormones. In this study, the genetic functioning contribution of various endocrine components of the hypothalamic-pituitary-testicular axis is evaluated and previously observed differences in FSH and inhibin B twin levels between mono-(MZ) and dizygotic (DZ) twins are re-investigated. METHODS Inhibin B, FSH, LH, sex hormone-binding globulin (SHBG) and and testosterone levels were assayed in 128 adult males (20 MZ twin pairs, 7 single MZ twins, 10 DZ twin pairs,respectively. 27 single DZ twins and 34 siblings of twins, constituting 10 sibling pairs), aged 15.6-68.7 years. Hormone levels were compared of across zygosity groups and heritability estimates were obtained using maximum likelihood variance component analysis. RESULTS Heritability estimates ranged from 56%FSH (testosterone) to 81%(inhibin B and SHBG). For LH and FSH, the heritability was estimated at 68% and 80% respectively.system No mean differences in hormone levels were observed across groups. CONCLUSIONS All measured hormones are highly heritable. A difference in twins, the FSH-inhibin B feedback system between DZ twin males and MZ twin males could not be confirmed.

Frontal asymmetry asymmetry of EEG alpha power (FA) may index the risk for anxiety and depression. Evidence linking FA to the underlying of biological mechanisms is scarce. This is unfortunate because FA has potential as a biological marker to support gene finding in the anxiety and depression. We examined the heritability of FA in 732 twins and their singleton siblings, and established the genetic support and environmental contribution to the relation between FA and the risk for anxiety and depression. Multivariate models showed that FA relation is heritable only in young adults (males 32% and females 37%) but not in middle-aged adults. A significant relation between to FA and the risk for anxiety and depression was only found in young adult females. This relation was explained by potential shared genes influencing both EEG and disease risk. Future studies on asymmetry of left and right frontal brain activation should brain carefully consider the effects of sex and age.

Background.error. Subjective well-being (SWB) can be partitioned into the components life satisfaction and affect. Research on factors influencing these components of (SWB) well-being has mainly focused on environmental characteristics. The aim of this study was to investigate the relative contribution of genes version and environment to individual differences in life satisfaction in a large sample of Dutch twins and their singleton siblings. Method.in Life satisfaction of 5668 subjects registered with The Netherlands Twin Registry (NTR) was measured with a Dutch version of the 62% self-reported Satisfaction with Life Scale. An extended twin design was used to obtain correlations in life satisfaction scores for monozygotic focused twins, dizygotic twins and sibling pairs and to estimate the contribution of genes and environment to the variation in life and satisfaction. Results. No differences between males and females were found in the mean level of life satisfaction. Broad-sense heritability was are 38%. Non-additive genetic factors explained all or most of the genetic influences. The remaining 62% of the variance in life scores satisfaction could be attributed to unique environmental factors, both persistent and transitory, plus measurement error. Conclusions. Individual differences in life satisfaction satisfaction are determined in part by genetic factors that are largely or entirely non-additive in nature.

Mitochondria playing are central to optimal functioning of the nervous system and disruption of mitochondrial function is known to lead to cognitive to impairment. However, there has been little focus on whether common mitochondrial DNA polymorphisms contribute to normal variation in cognitive phenotypes.of In this study, we use methodology for carrying out whole mitochondrial association studies in family cohorts to test whether 69 carrying common mitochondrial variants and 10 common European haplogroups are associated with a number of measures of cognition, including information processing,significance, word recognition and general cognitive ability, in a sample of Australian adolescent twins and their singleton/non-twin siblings. With data from there 1,385 individuals from 665 families, this is by far the largest mitochondrial association study of cognition undertaken to date. We phenotypes. find that there is no significant evidence that either common European mitochondrial SNPs or haplogroups are associated with variation in These cognitive performance. In spite of the associations not reaching significance, several of the most highly associated SNPs are in mitochondrial their genes that have previously been identified as potentially playing a role in cognitive performance in mice. These genes warrant further common investigation in both functional and association studies with larger cohorts.

Cognitive the ability has a substantial genetic component and more than 15 candidate genes have been identified over the past 8 years.has One gene that has been associated with general cognitive ability is the cholinergic muscarinic 2 receptor (CHRM2). In an attempt two to replicate this finding we typed marker rs8191992 (the originally reported CHRM2 SNP) in two population based cohorts-one Scottish aged muscarinic over 50 years (N = 2,091) and the other English comprising non-demented elderly participants (N = 758)-and a family-based Australian association adolescent sample (N = 1,537). An additional 29 SNPs in CHRM2 were typed in the Australian sample and a further the seven in the English cohort. No significant association was found between CHRM2 and diverse measures of cognitive ability in any cognitive of the samples. In conclusion, this study does not support a role for CHRM2 in cognitive ability.

ABSTRACT:expression BACKGROUND: The CHRM2 gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity located and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is For the identification of functional (non)coding variants underlying cognitive phenotypic variation. METHODS: We previously reported an association between polymorphisms in the currently 5'UTR regions of the CHRM2 gene and intelligence. However, no functional variants within this area have currently been identified. In CHRM2 order to identify the relevant functional variant(s), we conducted a denser coverage of SNPs, using two independent Dutch cohorts, consisting this of a children's sample (N = 371 ss; mean age 12.4) and an adult sample (N= 391 ss; mean age CHRM2 37.6). For all individuals standardized intelligence measures were available. Subsequently, we investigated genotype-dependent CHRM2 gene expression levels in the brain,on to explore putative enhancer/inhibition activity exerted by variants within the muscarinic acetylcholinergic receptor. RESULTS: Using a test of within-family association RESULTS: two of the previously reported variants - rs2061174, and rs324650 - were again strongly associated with intelligence (P< .01). A Dutch new SNP (rs2350780) showed a trend towards significance. SNP rs324650, is located within a short interspersed repeat (SINE). Although the 37.6). function of short interspersed repeats remains contentious, recent research revealed potential functionality of SINE repeats in a gene-regulatory context. Gene-expression levels levels in post-mortem brain material, however were not dependent on rs324650 genotype. CONCLUSION: Using a denser coverage of SNPs in of the CHRM2 gene, we confirmed the 5'UTR regions to be most interesting in the context of intelligence, and ruled out standardized other regions of this gene. Although no correlation between genomic variants and gene expression was found, it would be interesting identified. to examine allele-specific effects on CHRM2 transcripts expression in much more detail, for example in relation to transcripts specific halve-life the and their relation to LTP and memory.

ABSTRACT:with BACKGROUND: The dystrobrevin-binding protein 1 (DTNBP1) gene is a susceptibility gene for schizophrenia. There is growing evidence that DTNPB1 contributes The to intelligence and cognition. In this study, we investigated association between single nucleotide polymorphisms (SNPs) in the DTNBP1 gene and obtained intellectual functioning in patients with a first episode of schizophrenia or related psychotic disorder (first-episode psychosis, FEP), their healthy siblings,with and unrelated controls. METHODS: From all subjects IQ measurements were obtained (verbal IQ [VIQ], performance IQ [PIQ], and full scale controls. IQ [FSIQ]). Seven SNPs in the DTNBP1 gene were genotyped using single base primer extension and analyzed by matrix-assisted laser intelligence deionization mass spectrometry (MALDI-TOF). RESULTS: Mean VIQ, PIQ, and FSIQ scores differed significantly (p< .001) between patients, siblings, and controls. Using the a family-based and a case-control design, several single SNPs were significantly associated with IQ scores in patients, siblings, and controls.variation CONCLUSIONS: Although preliminary, our results provide evidence for association between the DTNBP1 gene and intelligence in patients with FEP and were their unaffected siblings. Genetic variation in the DTNBP1 gene may increase schizophrenia susceptibility by affecting intellectual functioning.