Evidence map›Paper›PMID 38076919›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Zoe Schmilovich, Vincent-Raphaël Bourque, Elise Douard, Guillaume Huguet, Cécile Poulain, Jay P Ross, Paria Alipour, Charles-Étienne Castonguay, Nadine Younis, Martineau Jean-Louis and 14 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 7 institutions in 2 countries.

Zoe SchmilovichDepartment of Human Genetics, McGill University, Montréal, QC, Canada.
Vincent-Raphaël BourqueCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Elise DouardCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Guillaume HuguetCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Cécile PoulainCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Jay P RossDepartment of Human Genetics, McGill University, Montréal, QC, Canada.
Paria AlipourDepartment of Human Genetics, McGill University, Montréal, QC, Canada.
Charles-Étienne CastonguayDepartment of Human Genetics, McGill University, Montréal, QC, Canada.
Nadine YounisDépartement de Pédiatrie, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Martineau Jean-LouisCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Zohra SaciCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Zdenka PausovaThe Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Tomas PausCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Gunter SchumanInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
David PorteousLothian Birth Cohorts group, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK.
Gail DaviesLothian Birth Cohorts group, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK.
Paul RedmondLothian Birth Cohorts group, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK.
Sarah E HarrisLothian Birth Cohorts group, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK.
Ian J DearyLothian Birth Cohorts group, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK.
Heather WhalleyGeneration Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, UK.
Caroline HaywardGeneration Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, UK.
Patrick A DionMontreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada.
Sébastien JacquemontCentre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada.
Guy A RouleauDepartment of Human Genetics, McGill University, Montréal, QC, Canada.
Centre Hospitalier Universitaire Sainte-Justine · CAMontreal Neurological Institute and Hospital · CAUniversity of Edinburgh · GBEdinburgh Cancer Research · GBUniversity of Toronto · CAKing's College London · GBUniversité de Montréal · CA

Funding

Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
A decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers R01DA049238 · NIDA · GEORGIA STATE UNIVERSITY · PI CALHOUN, VINCE D, LIU, JINGYU · 2019 to 2023
$2.9M
Axon, Testosterone and Mental Health during AdolescenceR01MH085772 · NIMH · BAYCREST CENTRE FOR GERIATRIC CARE · PI PAUS, TOMAS · 2010 to 2014
$1.5M
ENIGMA World Aging CenterR56AG058854 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2018
$683k
Medical Research Council MC_UU_00007/10NIA NIH HHS R56 AG058854NIBIB NIH HHS U54 EB020403NIDA NIH HHS R01 DA049238NIMH NIH HHS R01 MH085772Wellcome Trust
6 · The paper itself

Abstract

Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer risk for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD risk, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability. In a cohort of 8,426 subjects with ASD and 169,804 controls with cognitive assessments, we found that rare coding CNVs and PRS-IQ increased ASD risk, even after adjusting for their effects on cognitive ability. Bottom decile PRS-IQ and CNVs both decreased cognitive ability but had opposing effects on ASD risk. Models combining both classes of variants showed that the effects of rare CNVs and PRS-IQ on ASD risk and cognitive ability were largely additive, further suggesting that risk for ASD is conferred independently from its effects on cognitive ability. Despite imparting mostly additive effects on ASD risk, rare CNVs and PRS-IQ showed opposing effects on core and associated features and developmental history among subjects with ASD. Our findings suggest that cognitive ability itself may not be the factor driving the underlying risk for ASD conferred by these two classes of genomic variants. In other words, ASD risk and cognitive ability may be two distinct manifestations of CNVs and PRS-IQ. This study also highlights the challenge of understanding how genetic risk for ASD maps onto its dimensional traits.

Identifiers

PMID38076919
PMCPMC10705642
OpenAlexW4389204345

What OpenQuestion holds

Textmetadata
LicenceCC BY-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.