Evaluating the interrelations between the autism polygenic score and psychiatric family history in risk for autism

Schendel, Diana; Laursen, Thomas Munk; Albiñana, Clara; Vilhjálmsson, Bjarni J.; Ladd‐Acosta, Christine; Fallin, M. Danielle; Benke, Kelly S.; Lee, Brian; Grove, Jakob; Kalkbrenner, Amy E.; Ejlskov, Linda; Hougaard, David M.; Bybjerg‐Grauholm, Jonas; Bækvad‐Hansen, Marie; Børglum, Anders; Werge, Thomas; Nordentoft, Merete; Mortensen, Preben Bo; Agerbo, Esben

doi:10.1002/aur.2629

Cited by 11 publications

(14 citation statements)

References 40 publications

(48 reference statements)

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“…In our sample, autism PGS explained 1.8% of the variance in autism diagnostic status, which is somewhat lower than in the original GWAS, and furthermore, autism PGS was not significantly higher in individuals with autism diagnosis compared to those without (p = 0.46) in our study population, indicating low power. However, other studies based on the same discovery GWAS also found that autism PGS was only weakly related or even unrelated to autism diagnosis and psychiatric family history of autism (Jansen et al, 2020;Schendel et al, 2022). That rare genetic variants play an important role in the aetiology of autism (Geschwind & ZHANG ET AL.…”

Section: Autism Pgs and Ed Severitymentioning

confidence: 99%

Association of autism diagnosis and polygenic scores with eating disorder severity

Zhang

Birgegård

Fundin

et al. 2022

Euro Eating Disorders Rev

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Among individuals with eating disorders (ED), those with co‐occurring autism are often considered to have more severe presentations and poorer prognosis. However, previous findings have been contradictory and limited by small sample size and/or cross‐sectional assessment of autistic traits. We examine the hypothesis that autism diagnosis and autism polygenic score (PGS) are associated with increased ED severity in a large ED cohort using a broad range of ED severity indicators. Our cohort included 3189 individuals (64 males) born 1977–2000 with current or previous anorexia nervosa who participated in the Anorexia Nervosa Genetics Initiative‐Sweden (ANGI‐SE) and for whom genotypes and linkage to national registers were available. We identified 134 (4.2%) individuals with registered autism diagnoses. Individuals with confirmed autism diagnosis had significantly more severe ED across three sets of severity indicators. Some of the largest effects were found for the proportion of individuals who attempted suicide and who received tube feeding (higher in autism), and for the time spent in inpatient care (longer in autism). Results for autism PGS were not statistically significant. Adapting ED treatment to the needs of individuals with co‐occurring autism is an important research direction to improve treatment outcome in this group.

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Section: Autism Pgs and Ed Severitymentioning

confidence: 99%

Association of autism diagnosis and polygenic scores with eating disorder severity

Zhang

Birgegård

Fundin

et al. 2022

Euro Eating Disorders Rev

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“…Nine studies assessed the association between the autism polygenic score and autism diagnosis. Of these, seven reported a significant positive association 10,25,27,30,32,33,36 . Two studies, based on smaller samples than the ones that reported significant associations, reported no significant association 37,50 .…”

Section: Resultsmentioning

confidence: 99%

“…Two studies, based on smaller samples than the ones that reported significant associations, reported no significant association 37,50 . In addition, the autism polygenic score acted in a dose-dependent manner, where people in higher percentiles on average were more likely to be diagnosed with autism 10,36 .…”

Section: Resultsmentioning

confidence: 99%

“…In line, Antaki et al (2022) 114 showed that a genetic score containing a combination of common and rare genetic factors significantly increased statistical power over separate common and rare variant scores. Schendel et al (2022) 36 argue that psychiatric family history and polygenic scores only minimally correlate and should therefore be considered separate, mostly uncorrelated, measures of autism’s genetic etiology. Lastly, although we do not find significant sex differences in the association of the autism polygenic score with outcome variables, there is building evidence for a different genetic makeup for men and women with autism.…”

Section: Discussionmentioning

confidence: 99%

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A Systematic Review and Meta-Analysis: Research Using the Autism Polygenic Score

de Wit,

Morgan,

Libedinsky

et al. 2024

Preprint

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ObjectiveGenetic factors play a substantial role in the etiology of autism and its co-occurrence with other conditions and traits. The autism polygenic score, derived from the latest autism case-control meta-genome-wide association studies, captures some of the accumulated influence of common genetic variants on autism. We reviewed and meta-analyzed published studies that assessed the relationship between this autism polygenic score and autism diagnosis, and autistic, behavioral and neurobiological traits.MethodSystematically searching public databases, we identified 72 studies and > 750 outcome measures. Included studies received a quality assessment.ResultsThe majority of included studies were rated as good quality. The autism polygenic score was most strongly associated with autism diagnosis (meta-analyticr= .162, 95% CI .066 – .258). The autism polygenic score was also significantly associated with autistic traits but to a lesser degree than for autism (meta-analyticr= .042 (95% CI .004 – .081). Associations with other outcomes were inconsistent and meta-analytic effect sizes were generally small (medianr= .03).ConclusionWe conclude that the current autism polygenic score is consistently associated with autism diagnostic status and autistic traits, but overlap between autism and other traits and conditions is not, from publications to date, explained significantly by the autism polygenic score. When compared to other mental conditions, autism is phenotypically and etiologically heterogeneous, which might drive the relatively modest associations observed with the autism polygenic score to date.

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“…A 2022 U.S. survey found a 2.6% prevalence rate among Spanish-speaking families ( 37 ). Saito et al reported a prevalence of 3.22% for Japan ( 38 ), and Schendel et al reported that a lifetime incidence of autism in a Danish cohort ranged from 3.52 to 4.28% ( 39 ). By contrast, schizophrenia prevalence was 0.33% before 1990, and 0.51% after 2013 ( 40 ).…”

Section: The Extent Of Autism Heterogeneitymentioning

confidence: 99%

Heterogeneity thwarts autism explanatory power: A proposal for endophenotypes

Waterhouse

2022

Front. Psychiatry

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Many researchers now believe that autism heterogeneity is likely to include many disorders, but most research is based on samples defined by the DSM-5 Autism Spectrum Disorder (ASD) criteria. However, individuals diagnosed with autism have complex and varied biological causes for their symptoms. Therefore, autism is not a unitary biological entity. And although autism is significantly different from typical development, autism is not a unitary clinical disorder because diagnosed individuals vary in symptom patterns, comorbidities, biomarkers, and gene variants. The DSM-5 ASD criteria were designed to reduce heterogeneity, and there have been many other efforts to reduce autism heterogeneity including using more stringent clinical criteria, dividing autism into low and high functioning groups, creating subgroups, and by studying larger samples. However, to date these efforts have not been successful. Heterogeneity is extensive and remains unexplained, and no autism pathophysiology has been discovered. Most importantly, heterogeneity has hindered the explanatory power of the autism diagnosis to discover drug regimens and effective behavioral treatments. The paper proposes that possible transdiagnostic endophenotypes may reduce autism heterogeneity. Searching for transdiagnostic endophenotypes requires exploring autism symptoms outside of the framework of the DSM-5 autism diagnosis. This paper proposes that researchers relax diagnostic criteria to increase the range of phenotypes to support the search for transdiagnostic endophenotypes. The paper proposes possible candidates for transdiagnostic endophenotypes. These candidates are taken from DSM-5 ASD criteria, from concepts that have resulted from researched theories, and from symptoms that are the result of subtyping. The paper then sketches a possible basis for a future transdiagnostic endophenotypes screening tool that includes symptoms of autism and other neurodevelopmental disorders.

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Evaluating the interrelations between the autism polygenic score and psychiatric family history in risk for autism

Cited by 11 publications

References 40 publications

Association of autism diagnosis and polygenic scores with eating disorder severity

Association of autism diagnosis and polygenic scores with eating disorder severity

A Systematic Review and Meta-Analysis: Research Using the Autism Polygenic Score

Heterogeneity thwarts autism explanatory power: A proposal for endophenotypes

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