Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population.


:Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few studies have examined the genetic overlap between cognitive ability and ASD/ADHD. The aim of this study was to examine the polygenic overlap between ASD/ADHD and cognitive ability in individuals from the general population. Polygenic risk for ADHD and ASD was calculated from genome-wide association studies of ASD and ADHD conducted by the Psychiatric Genetics Consortium. Risk scores were created in three independent cohorts: Generation Scotland Scottish Family Health Study (GS:SFHS) (n=9863), the Lothian Birth Cohorts 1936 and 1921 (n=1522), and the Brisbane Adolescent Twin Sample (BATS) (n=921). We report that polygenic risk for ASD is positively correlated with general cognitive ability (beta=0.07, P=6 × 10(-7), r(2)=0.003), logical memory and verbal intelligence in GS:SFHS. This was replicated in BATS as a positive association with full-scale intelligent quotient (IQ) (beta=0.07, P=0.03, r(2)=0.005). We did not find consistent evidence that polygenic risk for ADHD was associated with cognitive function; however, a negative correlation with IQ at age 11 years (beta=-0.08, Z=-3.3, P=0.001) was observed in the Lothian Birth Cohorts. These findings are in individuals from the general population, suggesting that the relationship between genetic risk for ASD and intelligence is partly independent of clinical state. These data suggest that common genetic variation relevant for ASD influences general cognitive ability.


Mol Psychiatry


Molecular psychiatry


Clarke TK,Lupton MK,Fernandez-Pujals AM,Starr J,Davies G,Cox S,Pattie A,Liewald DC,Hall LS,MacIntyre DJ,Smith BH,Hocking LJ,Padmanabhan S,Thomson PA,Hayward C,Hansell NK,Montgomery GW,Medland SE,Martin NG,Wright MJ




Has Abstract


2016-03-01 00:00:00














  • Depressive disorder moderates the effect of the FTO gene on body mass index.

    abstract::There is evidence that obesity-related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to body mass ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,meta分析


    authors: Rivera M,Cohen-Woods S,Kapur K,Breen G,Ng MY,Butler AW,Craddock N,Gill M,Korszun A,Maier W,Mors O,Owen MJ,Preisig M,Bergmann S,Tozzi F,Rice J,Rietschel M,Rucker J,Schosser A,Aitchison KJ,Uher R,Craig IW,Lewis

    更新日期:2012-06-01 00:00:00

  • The symptom network structure of depressive symptoms in late-life: Results from a European population study.

    abstract::The network theory conceptualizes mental disorders as complex networks of symptoms influencing each other by creating feedback loops, leading to a self-sustained syndromic constellation. Symptoms central to the network have the greatest impact in sustaining the rest of symptoms. This analysis focused on the network st...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Belvederi Murri M,Amore M,Respino M,Alexopoulos GS

    更新日期:2020-07-01 00:00:00

  • Traumatic stress, oxidative stress and post-traumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis.

    abstract::Post-traumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellula...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审


    authors: Miller MW,Sadeh N

    更新日期:2014-11-01 00:00:00

  • A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease.

    abstract::Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide subs...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Kunugi H,Ueki A,Otsuka M,Isse K,Hirasawa H,Kato N,Nabika T,Kobayashi S,Nanko S

    更新日期:2001-01-01 00:00:00

  • Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.

    abstract::Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Martinez ME,Duarte CW,Stohn JP,Karaczyn A,Wu Z,DeMambro VE,Hernandez A

    更新日期:2020-05-01 00:00:00

  • ADORA1-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism.

    abstract::It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripher...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Zhang J,Hou Y,Du XL,Chen D,Sui G,Qi Y,Licinio J,Wong ML,Yang Y

    更新日期:2020-10-16 00:00:00

  • CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia.

    abstract::To examine the cannabinoid hypothesis for pathogenesis of schizophrenia, we examined two kinds of polymorphisms of the CNR1 gene, which encodes human CB1 receptor, a subclass of central cannabinoid receptors, in schizophrenics and age-matched controls in the Japanese population. Allelic and genotypic distributions of ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Ujike H,Takaki M,Nakata K,Tanaka Y,Takeda T,Kodama M,Fujiwara Y,Sakai A,Kuroda S

    更新日期:2002-01-01 00:00:00

  • CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies.

    abstract::Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (C...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Gray LR,Cowley D,Welsh C,Lu HK,Brew BJ,Lewin SR,Wesselingh SL,Gorry PR,Churchill MJ

    更新日期:2016-04-01 00:00:00

  • Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

    abstract::The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Heidari M,Johnstone DM,Bassett B,Graham RM,Chua AC,House MJ,Collingwood JF,Bettencourt C,Houlden H,Ryten M,Olynyk JK,Trinder D,Milward EA

    更新日期:2016-11-01 00:00:00

  • Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model.

    abstract::Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN-/-) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cogniti...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Ng RC,Jian M,Ma OK,Bunting M,Kwan JS,Zhou GJ,Senthilkumar K,Iyaswamy A,Chan PK,Li M,Leung KM,Kumar Durairajan SS,Lam KS,Chu LW,Festenstein R,Chung SK,Chan KH

    更新日期:2020-03-04 00:00:00

  • How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials.

    abstract::We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,meta分析,评审


    authors: Leucht S,Arbter D,Engel RR,Kissling W,Davis JM

    更新日期:2009-04-01 00:00:00

  • BDNF gene is a risk factor for schizophrenia in a Scottish population.

    abstract::Schizophrenia is a severe psychiatric disease with a strong genetic component. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar (BP) disorders. The present study has examined two polymorphisms in linkage disequilibrium in the BDNF gene, which have been vario...

    journal_title:Molecular psychiatry

    pub_type: 临床试验,杂志文章


    authors: Neves-Pereira M,Cheung JK,Pasdar A,Zhang F,Breen G,Yates P,Sinclair M,Crombie C,Walker N,St Clair DM

    更新日期:2005-02-01 00:00:00

  • Correction to: Psychiatric genetics and the structure of psychopathology.

    abstract::In the Table 1 legend, the reference numbers and symbols were not correctly presented in the footnotes. The corrected footnotes are presented below. ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,已发布勘误


    authors: Smoller JW,Andreassen OA,Edenberg HJ,Faraone SV,Glatt SJ,Kendler KS

    更新日期:2019-03-01 00:00:00

  • An epigenome-wide association study meta-analysis of educational attainment.

    abstract::The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date i...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,meta分析


    authors: Karlsson Linnér R,Marioni RE,Rietveld CA,Simpkin AJ,Davies NM,Watanabe K,Armstrong NJ,Auro K,Baumbach C,Bonder MJ,Buchwald J,Fiorito G,Ismail K,Iurato S,Joensuu A,Karell P,Kasela S,Lahti J,McRae AF,Mandaviya PR,Se

    更新日期:2017-12-01 00:00:00

  • Cocaine and sucrose rewards recruit different seeking ensembles in the nucleus accumbens core.

    abstract::Poorly regulated reward seeking is a central feature of substance use disorder. Recent research shows that rewarding drug-related experiences induce synchronous activation of a discrete number of neurons in the nucleus accumbens that are causally linked to reward-related contexts. Here we comprehensively characterize ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Bobadilla AC,Dereschewitz E,Vaccaro L,Heinsbroek JA,Scofield MD,Kalivas PW

    更新日期:2020-12-01 00:00:00

  • Variants in Apaf-1 segregating with major depression promote apoptosome function.

    abstract::APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 ac...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Harlan J,Chen Y,Gubbins E,Mueller R,Roch JM,Walter K,Lake M,Olsen T,Metzger P,Dorwin S,Ladror U,Egan DA,Severin J,Johnson RW,Holzman TF,Voelp K,Davenport C,Beck A,Potter J,Gopalakrishnan M,Hahn A,Spear BB,Halb

    更新日期:2006-01-01 00:00:00

  • Interrogating the mouse thalamus to correct human neurodevelopmental disorders.

    abstract::While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how ba...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审


    authors: Schmitt LI,Halassa MM

    更新日期:2017-02-01 00:00:00

  • A genome-wide linkage study of individuals with high scores on NEO personality traits.

    abstract::The NEO-Five-Factor Inventory divides human personality traits into five dimensions: neuroticism, extraversion, openness, conscientiousness and agreeableness. In this study, we sought to identify regions harboring genes with large effects on the five NEO personality traits by performing genome-wide linkage analysis of...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Amin N,Schuur M,Gusareva ES,Isaacs A,Aulchenko YS,Kirichenko AV,Zorkoltseva IV,Axenovich TI,Oostra BA,Janssens AC,van Duijn CM

    更新日期:2012-10-01 00:00:00

  • Advances in molecular genetics of panic disorder.

    abstract::The molecular genetic research on panic disorder (PD) has grown tremendously in the past decade. Although the data from twin and family studies suggest an involvement of genetic factors in the familial transmission of PD with the heritability estimate near 40%, the genetic substrate underlying panicogenesis is not yet...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审


    authors: Maron E,Hettema JM,Shlik J

    更新日期:2010-07-01 00:00:00

  • GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons.

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    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Chien T,Weng YT,Chang SY,Lai HL,Chiu FL,Kuo HC,Chuang DM,Chern Y

    更新日期:2018-12-01 00:00:00

  • Genetic association of acyl-coenzyme A: cholesterol acyltransferase with cerebrospinal fluid cholesterol levels, brain amyloid load, and risk for Alzheimer's disease.

    abstract::A common polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1), which is involved in the regulation of beta-amyloid peptide generation, is associated with low brain amyloid load (P=0.03) and with low cerebrospinal fluid levels of cholesterol (P=0.005). This polymorphism of SOAT1 is a...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Wollmer MA,Streffer JR,Tsolaki M,Grimaldi LM,Lütjohann D,Thal D,von Bergmann K,Nitsch RM,Hock C,Papassotiropoulos A

    更新日期:2003-06-01 00:00:00

  • Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.

    abstract::Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,多中心研究


    authors: Schwab SG,Knapp M,Sklar P,Eckstein GN,Sewekow C,Borrmann-Hassenbach M,Albus M,Becker T,Hallmayer JF,Lerer B,Maier W,Wildenauer DB

    更新日期:2006-09-01 00:00:00

  • A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication.

    abstract::Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started wi...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Arcos-Burgos M,Jain M,Acosta MT,Shively S,Stanescu H,Wallis D,Domené S,Vélez JI,Karkera JD,Balog J,Berg K,Kleta R,Gahl WA,Roessler E,Long R,Lie J,Pineda D,Londoño AC,Palacio JD,Arbelaez A,Lopera F,Elia J,Hakon

    更新日期:2010-11-01 00:00:00

  • Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism.

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    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Desai A,Sequeira JM,Quadros EV

    更新日期:2017-09-01 00:00:00

  • Time-delimited signaling of MET receptor tyrosine kinase regulates cortical circuit development and critical period plasticity.

    abstract::Normal development of cortical circuits, including experience-dependent cortical maturation and plasticity, requires precise temporal regulation of gene expression and molecular signaling. Such regulation, and the concomitant impact on plasticity and critical periods, is hypothesized to be disrupted in neurodevelopmen...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Chen K,Ma X,Nehme A,Wei J,Cui Y,Cui Y,Yao D,Wu J,Anderson T,Ferguson D,Levitt P,Qiu S

    更新日期:2020-01-03 00:00:00

  • Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors.

    abstract::The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is defici...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Brody SA,Dulawa SC,Conquet F,Geyer MA

    更新日期:2004-01-01 00:00:00

  • Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.

    abstract::Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to de...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Maycox PR,Kelly F,Taylor A,Bates S,Reid J,Logendra R,Barnes MR,Larminie C,Jones N,Lennon M,Davies C,Hagan JJ,Scorer CA,Angelinetta C,Akbar MT,Hirsch S,Mortimer AM,Barnes TR,de Belleroche J

    更新日期:2009-12-01 00:00:00

  • Reversal of synaptic and behavioral deficits in a 16p11.2 duplication mouse model via restoration of the GABA synapse regulator Npas4.

    abstract::The human 16p11.2 gene locus is a hot spot for copy number variations, which predispose carriers to a range of neuropsychiatric phenotypes. Microduplications of 16p11.2 are associated with autism spectrum disorder (ASD), intellectual disability (ID), and schizophrenia (SZ). Despite the debilitating nature of 16p11.2 d...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Rein B,Tan T,Yang F,Wang W,Williams J,Zhang F,Mills A,Yan Z

    更新日期:2020-02-25 00:00:00

  • FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications.

    abstract::Psychotropic medications target glycogen synthase kinase 3β (GSK3β), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3β at serine 9 (pGSK3β(S9))....

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Gassen NC,Hartmann J,Zannas AS,Kretzschmar A,Zschocke J,Maccarrone G,Hafner K,Zellner A,Kollmannsberger LK,Wagner KV,Mehta D,Kloiber S,Turck CW,Lucae S,Chrousos GP,Holsboer F,Binder EB,Ising M,Schmidt MV,Rein T

    更新日期:2016-02-01 00:00:00

  • Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness.

    abstract::Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alon...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Petersen N,Kearley NW,Ghahremani DG,Pochon JB,Fry ME,Rapkin AJ,London ED

    更新日期:2021-01-08 00:00:00