Examining the bidirectional association between emotion recognition and autistic traits using observational and genetic analyses

AbstractBackgroundThere is mixed evidence for an association between autism spectrum disorder (ASD) and emotion recognition deficits. We sought to assess the bidirectionality of this association using phenotypic and genetic data in a large community sample.MethodsAnalyses were conducted in three stages. First, we examined the bidirectional association between autistic traits at age 8 years and emotion recognition task (ERT) responses at age 24 years (Study 1; N=3,562); and between Diagnostic Analysis of Non-Verbal Accuracy (DANVA) emotion recognition responses at age 8 years and autistic traits at age 10 years (Study 2; N=9,071). Next, we used genetic analyses (Study 3) to examine the association between polygenic risk scores for ASD and these phenotypes. The genetic correlation between ASD and ERT responses at age 24 was also estimated. Analyses were conducted in the Avon Longitudinal Study of Parents and Children.ResultsAutistic traits at age 8 years were negatively associated with later total correct responses on ERT in Study 1 (b=-0.18; 95% CI: −0.27 to −0.09). We also found evidence of an association in Study 2 (b=-0.04; 95% CI: −0.05 to −0.03). We found the opposite association i.e., positive, between the ASD polygenic risk score and ERT (b=0.40; 95% CI: 0.10 to 0.70); however, this association varied across different p-value thresholds so should be interpreted with caution. We did not find evidence of a genetic correlation between ASD and ERT.ConclusionWe found an observational association between poorer emotion recognition and increased autistic traits. Our genetic analyses revealed an association between ASD polygenic risk and the ERT outcome, which may suggest a shared genetic aetiology between these or a potential causal pathway. Our results may inform interventions targeting emotion recognition.

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Examining the bidirectional association between emotion recognition and social autistic traits using observational and genetic analyses

Journal of Child Psychology and Psychiatry ◽

10.1111/jcpp.13395 ◽

2021 ◽

Author(s):

Zoe E. Reed ◽

Liam Mahedy ◽

Abigail Jackson ◽

George Davey Smith ◽

Ian Penton‐Voak ◽

...

Keyword(s):

Emotion Recognition ◽

Autistic Traits ◽

Genetic Analyses ◽

Bidirectional Association

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Polygenic Risk Scores Augment Stroke Subtyping

Neurology Genetics ◽

10.1212/nxg.0000000000000560 ◽

2021 ◽

Vol 7 (2) ◽

pp. e560

Author(s):

Jiang Li ◽

Durgesh P. Chaudhary ◽

Ayesha Khan ◽

Christoph Griessenauer ◽

David J. Carey ◽

...

Keyword(s):

Ischemic Stroke ◽

Genetic Correlation ◽

Genome Wide Association Study ◽

Low Frequency ◽

European Ancestry ◽

Risk Scores ◽

Polygenic Risk Score ◽

Large Artery ◽

Polygenic Risk ◽

Gene Sets

ObjectiveTo determine whether the polygenic risk score (PRS) derived from MEGASTROKE is associated with ischemic stroke (IS) and its subtypes in an independent tertiary health care system and to identify the PRS derived from gene sets of known biological pathways associated with IS.MethodsControls (n = 19,806/7,484, age ≥69/79 years) and cases (n = 1,184/951 for discovery/replication) of acute IS with European ancestry and clinical risk factors were identified by leveraging the Geisinger Electronic Health Record and chart review confirmation. All Geisinger MyCode patients with age ≥69/79 years and without any stroke-related diagnostic codes were included as low risk control. Genetic heritability and genetic correlation between Geisinger and MEGASTROKE (EUR) were calculated using the summary statistics of the genome-wide association study by linkage disequilibrium score regression. All PRS for any stroke (AS), any ischemic stroke (AIS), large artery stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS) were constructed by PRSice-2.ResultsA moderate heritability (10%–20%) for Geisinger sample as well as the genetic correlation between MEGASTROKE and the Geisinger cohort was identified. Variation of all 5 PRS significantly explained some of the phenotypic variations of Geisinger IS, and the R2 increased by raising the cutoff for the age of controls. PRSLAS, PRSCES, and PRSSVS derived from low-frequency common variants provided the best fit for modeling (R2 = 0.015 for PRSLAS). Gene sets analyses highlighted the association of PRS with Gene Ontology terms (vascular endothelial growth factor, amyloid precursor protein, and atherosclerosis). The PRSLAS, PRSCES, and PRSSVS explained the most variance of the corresponding subtypes of Geisinger IS suggesting shared etiologies and corroborated Geisinger TOAST subtyping.ConclusionsWe provide the first evidence that PRSs derived from MEGASTROKE have value in identifying shared etiologies and determining stroke subtypes.

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Right Posterior Insula and Putamen Volume Mediate the Effect of Oxytocin Receptor Polygenic Risk for Autism Spectrum Disorders on Reward Dependence in Healthy Adults

Cerebral Cortex ◽

10.1093/cercor/bhaa198 ◽

2020 ◽

Author(s):

Junping Wang ◽

Peng Zhang ◽

Wei Li ◽

Qin Wen ◽

Feng Liu ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Personality Trait ◽

Autism Spectrum ◽

Oxytocin Receptor ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Reward Dependence ◽

Posterior Insula ◽

Spectrum Disorders ◽

The Right

Abstract Much evidence indicates the influence of the oxytocin receptor (OXTR) gene on autism spectrum disorders (ASDs), a set of disorders characterized by a range of deficits in prosocial behaviors, which are closely related to the personality trait of reward dependence (RD). However, we do not know the effect of the OXTR polygenic risk score for ASDs (OXTR-PRSASDs) on RD and its underlying neuroanatomical substrate. Here, we aimed to investigate associations among the OXTR-PRSASDs, gray matter volume (GMV), and RD in two independent datasets of healthy young adults (n = 450 and 540). We found that the individuals with higher OXTR-PRSASDs had lower RD and significantly smaller GMV in the right posterior insula and putamen. The GMV of this region showed a positive correlation with RD and a mediation effect on the association between OXTR-PRSASDs and RD. Moreover, the correlation map between OXTR-PRSASDs and GMV showed spatial correlation with OXTR gene expression. All results were highly consistent between the two datasets. These findings highlight a possible neural pathway by which the common variants in the OXTR gene associated with ASDs may jointly impact the GMV of the right posterior insula and putamen and further affect the personality trait of RD.

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Speeded reasoning moderates the inverse relationship between autistic traits and emotion recognition

Autism ◽

10.1177/1362361320937090 ◽

2020 ◽

Vol 24 (8) ◽

pp. 2304-2309 ◽

Cited By ~ 1

Author(s):

Alex Bertrams ◽

Katja Schlegel

Keyword(s):

Information Processing ◽

Emotion Recognition ◽

Inverse Relationship ◽

Recognition Performance ◽

Autistic Traits ◽

Autism Spectrum ◽

Reasoning Ability ◽

Underlying Assumption ◽

Reasoning Test ◽

Autistic People

People with diagnosed autism or being high in autistic traits have been found to have difficulties with recognizing emotions from nonverbal expressions. In this study, we investigated whether speeded reasoning (reasoning performance under time pressure) moderates the inverse relationship between autistic traits and emotion recognition performance. We expected the negative correlation between autistic traits and emotion recognition to be less strong when speeded reasoning was high. The underlying assumption is that people high in autistic traits can compensate for their low intuition in recognizing emotions through quick analytical information processing. A paid online sample ( N = 217) completed the 10-item version of the Autism Spectrum Quotient, two emotion recognition tests using videos with sound (Geneva Emotion Recognition Test) and pictures (Reading the Mind in the Eyes Test), and Baddeley’s Grammatical Reasoning Test to measure speeded reasoning. As expected, the inverse relationship between autistic traits and emotion recognition performance was less pronounced for individuals with high compared to low speeded reasoning ability. These results suggest that a high ability in making quick mental inferences may (partly) compensate for difficulties with intuitive emotion recognition related to autistic traits. Lay abstract Autistic people typically have difficulty recognizing other people’s emotions and to process nonverbal cues in an automatic, intuitive fashion. This usually also applies to people who—regardless of an official diagnosis of autism—achieve high values in autism questionnaires. However, some autistic people do not seem to have any problems with emotion recognition. One explanation may be that these individuals are able to compensate for their lack of intuitive or automatic processing through a quick conscious and deliberate analysis of the emotional cues in faces, voices, and body movements. On these grounds, we assumed that the higher autistic people’s ability to reason quickly (i.e. to make quick logical inferences), the fewer problems they should have with determining other people’s emotions. In our study, we asked workers on the crowdsourcing marketplace MTurk to complete a questionnaire about their autistic traits, to perform emotion recognition tests, and to complete a test of the ability to reason under time constraints. In our sample of 217 people, we found the expected pattern. Overall, those who had higher values in the autism questionnaire scored lower in the emotion recognition tests. However, when reasoning ability was taken into account, a more nuanced picture emerged: participants with high values both on the autism questionnaire and on the reasoning test recognized emotions as well as individuals with low autistic traits. Our results suggest that fast analytic information processing may help autistic people to compensate problems in recognizing others’ emotions.

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Erratum: Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs)

Journal of Human Genetics ◽

10.1038/jhg.2009.19 ◽

2009 ◽

Vol 54 (3) ◽

pp. 191-191

Author(s):

Takeshi Nishiyama ◽

Hiroko Taniai ◽

Taishi Miyachi ◽

Koken Ozaki ◽

Makoto Tomita ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Genetic Correlation ◽

Autistic Traits ◽

Population Based ◽

Autism Spectrum ◽

Spectrum Disorders

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Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization

Molecular Psychiatry ◽

10.1038/s41380-021-01204-z ◽

2021 ◽

Author(s):

Zhiqiang Sha ◽

Dick Schijven ◽

Clyde Francks

Keyword(s):

Sex Differences ◽

Executive Functions ◽

Autism Spectrum ◽

Brain Asymmetry ◽

Risk Scores ◽

Polygenic Risk Score ◽

Imaging Data ◽

Polygenic Risk ◽

Left Right Asymmetry ◽

The Uk

AbstractAutism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing vs. empathizing cognitive styles, with resemblances to male vs. female average sex differences. Left–right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness, and subcortical volume measures in 32,256 participants from the UK Biobank. Polygenic risks for the two disorders were positively correlated (r = 0.08, p = 7.13 × 10−50) and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each polygenic risk score was associated with multivariate brain asymmetry after adjusting for sex, ASD r = 0.03, p = 2.17 × 10−9, and schizophrenia r = 0.04, p = 2.61 × 10−11, but the multivariate patterns were mostly distinct for the two polygenic risks and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both polygenic risks were associated with asymmetries of regions important for language and executive functions, consistent with behavioral associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risks for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.

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Genetic liability to rheumatoid arthritis on autism and autistic traits: polygenic risk score and Mendelian randomization analyses

Translational Psychiatry ◽

10.1038/s41398-021-01772-2 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Amanda Ly ◽

Beate Leppert ◽

Dheeraj Rai ◽

Hannah Jones ◽

Christina Dardani ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mendelian Randomization ◽

Causal Effect ◽

Autistic Traits ◽

Causal Effects ◽

Risk Scores ◽

Polygenic Risk Score ◽

Genetic Liability ◽

Polygenic Risk ◽

Genome Wide

AbstractHigher prevalence of autism in offspring born to mothers with rheumatoid arthritis has been reported in observational studies. We investigated (a) the associations between maternal and offspring’s own genetic liability for rheumatoid arthritis and autism-related outcomes in the offspring using polygenic risk scores (PRS) and (b) whether the effects were causal using Mendelian randomization (MR). Using the latest genome-wide association (GWAS) summary data on rheumatoid arthritis and individual-level data from the Avon Longitudinal Study of Parents and Children, United Kingdom, we constructed PRSs for maternal and offspring genetic liability for rheumatoid arthritis (single-nucleotide polymorphism [SNP] p-value threshold 0.05). We investigated associations with autism, and autistic traits: social and communication difficulties, coherence, repetitive behaviours and sociability. We used modified Poisson regression with robust standard errors. In two-sample MR analyses, we used 40 genome-wide significant SNPs for rheumatoid arthritis and investigated the causal effects on risk for autism, in 18,381 cases and 27,969 controls of the Psychiatric Genetics Consortium and iPSYCH. Sample size ranged from 4992 to 7849 in PRS analyses. We found little evidence of associations between rheumatoid arthritis PRSs and autism-related phenotypes in the offspring (maternal PRS on autism: RR 0.89, 95%CI 0.73–1.07, p = 0.21; offspring’s own PRS on autism: RR 1.11, 95%CI 0.88–1.39, p = 0.39). MR results provided little evidence for a causal effect (IVW OR 1.01, 95%CI 0.98–1.04, p = 0.56). There was little evidence for associations between genetic liability for rheumatoid arthritis on autism-related outcomes in offspring. Lifetime risk for rheumatoid arthritis has no causal effects on autism.

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Investigating the source of increased bipolar and major depressive disorder polygenic risk in multiplex schizophrenia families

10.1101/2021.11.15.21266368 ◽

2021 ◽

Author(s):

Mohammad Ahangari ◽

Robert Kirkpatrick ◽

Tan-Hoang Nguyen ◽

Nathan Gillespie ◽

Irish Schizophrenia Genomics Consortium ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Psychiatric Disorders ◽

Genetic Correlation ◽

Affective Disorders ◽

Genetic Factors ◽

Genetic Correlations ◽

Polygenic Risk Score ◽

Major Depressive ◽

Polygenic Risk

Psychotic and affective disorders often aggregate in the relatives of probands with schizophrenia (SCZ), and genetic studies show substantial genetic correlation among SCZ, bipolar disorder (BIP) and major depressive disorder (MDD). However, the nature of this genetic overlap in polygenic risk score (PRS) analyses of multiplex families has not been fully dissected. In the current study, we investigated the polygenic risk burden of BIP and MDD in a sample of 257 multiplex SCZ families (N=1,005) and population controls (N=2,205). Furthermore, due to the strong genetic correlation among SCZ, BIP, and MDD, we examined whether increased BIP or MDD PRS in members of multiplex SCZ families can be attributed to latent genetic factors unique to BIP or MDD, or latent genetic factors that each of these two disorders share with SCZ. Our results indicate that members of multiplex SCZ families have an increased PRS for BIP and MDD, however, this observation is largely attributable to latent genetic factors that BIP or MDD share with SCZ, rather than latent genetic factors unique to them. These results provide new insight for cross-disorder PRS analyses of psychiatric disorders, by cautioning that for complete interpretation of observed cross-disorder PRS enrichment, we should account for genetic correlations across psychiatric disorders. Our findings further indicates that members of multiplex SCZ families may have an increased genetic vulnerability to both psychotic and affective disorders, and for full assessment of an individual genetic risk, familial backgrounds should be taken into consideration.

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