Polygenic scores for autism are associated with reduced neurite density in adults and children from the general population

被引：0

作者：

Gu, Yuanjun ^{[1
,2
]}

Maria-Stauffer, Eva ^{[1
]}

Bedford, Saashi A. ^{[1
,2
]}

Adhya, Deep ^{[2
,11
]}

Allison, Carrie ^{[2
]}

Ayeung, Bonnie ^{[12
,13
]}

Bamford, Rosie ^{[14
]}

Bethlehem, Richard ^{[10
]}

Biron-Shental, Tal ^{[15
]}

Burton, Graham ^{[16
]}

Davies, Jonathan ^{[17
]}

Davis, Joanna ^{[2
]}

Floris, Dori ^{[18
,19
,20
]}

Franklin, Alice ^{[17
]}

Gabis, Lidia ^{[21
]}

Geschwind, Daniel ^{[22
,23
,24
,25
]}

Greenberg, David M. ^{[2
]}

Havdahl, Alexandra ^{[26
,27
,28
]}

Heazell, Alexander ^{[29
,30
]}

Holt, Rosemary ^{[2
]}

Hurles, Matthew ^{[9
]}

Khan, Yumnah ^{[1
,2
]}

Lai, Meng-Chuan ^{[2
,31
,32
,33
,34
,35
,36
]}

Lancaster, Madeline ^{[11
,37
]}

Lombardo, Michael ^{[2
,38
]}

Martinez, Jose Gonzalez ^{[39
]}

Mill, Jonathan ^{[14
]}

Musa, Mahmoud Koko ^{[9
]}

Niakan, Kathy ^{[11
,16
,40
,41
]}

Pavlinek, Adam ^{[42
,43
]}

Polit, Lucia Dutan ^{[43
]}

Radecki, Marcin ^{[2
,44
]}

Rowitch, David ^{[45
]}

Sichlinger, Laura ^{[42
,43
,46
]}

Srivastava, Deepak ^{[42
,43
]}

Tsompanidis, Alexandros ^{[2
]}

Uzefovsky, Florina ^{[47
]}

Weir, Elizabeth ^{[2
]}

Zhang, Xinhe ^{[1
,2
]}

Borglum, Anders ^{[4
,5
,6
,7
]}

Bybjerg-Grauholm, Jonas ^{[48
]}

Hougaard, David M. ^{[48
]}

Mors, Ole ^{[4
,49
]}

Mortensen, Preben Bo ^{[4
,50
]}

Nordentoft, Merete ^{[4
,51
,52
]}

Werge, Thomas ^{[4
,52
,53
]}

Romero-Garcia, Rafael ^{[1
,3
]}

Grove, Jakob ^{[4
,5
,6
,7
,8
]}

Borglum, Anders D. ^{[4
,5
,6
,7
]}

Martin, Hilary ^{[9
]}

机构：

[1] Univ Cambridge, Dept Psychiat, Cambridge CB2 8AH, England

[2] Univ Cambridge, Autism Res Ctr, Dept Psychiat, Cambridge CB2 8AH, England

[3] Univ Seville, Inst Biomed Sevilla IBiS, HUVR, HUVR,CSIC,CIBERSAM,ISCIII, ES-41013 Seville, Spain

[4] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark

[5] Aarhus Univ, Ctr Genom & Personalized Med CGPM, DK-8000 Aarhus, Denmark

[6] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[7] Aarhus Univ, iSEQ Ctr, DK-8000 Aarhus, Denmark

[8] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus, Denmark

[9] Wellcome Sanger Inst, Wellcome Genome Campus, Hinxton CB1 01SA, Cambs, England

[10] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England

[11] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England

[12] Univ Cambridge, Cambridge, England

[13] Univ Cambridge, Autism Res Ctr, Cambridge, England

[14] Univ Exeter, Univ Exeter Med Sch, Inst Biomed & Clin Sci, Barrack Rd, Exeter EX2 5DW, England

[15] Tel Aviv Univ, Sch Med, Meir Med Ctr, Tel Aviv, Israel

[16] Univ Cambridge, Loke Ctr Trophoblast Res, Dept Physiol Dev & Neurosci, Cambridge, England

[17] Univ Exeter, Univ Exeter Med Sch, Coll Med & Hlth, Exeter, England

[18] Univ Zurich, Dept Psychol, Methods Plast Res, Zurich, Switzerland

[19] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[20] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands

[21] Maccabi Healthcare Serv, Child Dev, Tel Aviv, Israel

[22] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA

[23] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

[24] Univ Calif Los Angeles, Semel Inst, Ctr Autism Res & Treatment, David Geffen Sch Med, Los Angeles, CA 90095 USA

[25] Univ Calif Los Angeles, Semel Inst, David Geffen Sch Med, Program Neurobehav Genet, Los Angeles, CA 90095 USA

[26] Univ Oslo, Dept Psychol, Oslo, Norway

[27] Lovisenberg Diaconal Hosp, Nic Waals Inst, Oslo, Norway

[28] Norwegian Inst Publ Hlth, PsychGen Ctr Genet Epidemiol & Mental Hlth, Oslo, Norway

[29] Univ Manchester, Maternal & Fetal Hlth Res Ctr, Sch Med Sci Med & Hlth, Manchester, England

[30] Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Manchester, England

[31] Campbell Family Mental Hlth Res Inst, Ctr Addict & Mental Hlth, Toronto, ON, Canada

[32] Hosp Sick Children, Dept Psychiat, Toronto, ON, Canada

[33] Univ Toronto, Temerty Fac Med, Dept Psychiat, Toronto, ON, Canada

[34] Univ Toronto, Fac Arts & Sci, Dept Psychol, Toronto, ON, Canada

[35] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei, Taiwan

[36] Coll Med, Taipei, Taiwan

[37] Cambridge Biomed Campus, MRC Lab Mol Biol, Francis Crick Ave, Cambridge, England

[38] Ist Italiano Tecnol, Ctr Neurosci & Cognit Syst UniTn, Lab Autism & Neurodev Disorders, Rovereto, Italy

[39] Spanish Natl Canc Res Ctr CNIO Madrid, Cell Div & Canc Grp, Madrid, Spain

[40] Francis Crick Inst, Human Embryo & Stem Cell Lab, London NW1 1AT, England

[41] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England

[42] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England

[43] Kings Coll London, MRC Ctr Neurodev Disorders, London, England

[44] IMT Sch Adv Studies Lucca, Social & Affect Neurosci Grp, Lucca, Italy

[45] Univ Cambridge, Dept Psychol, Cambridge, England

[46] Kings Coll London, Fac Life Sci & Med, London, England

[47] Bengurion Univ, Dept Psychol, Beer Sheva, Israel

[48] Statens Serum Inst, Danish Ctr Neonatal Screening, Dept Congenital Disorders, Copenhagen, Denmark

[49] Aarhus Univ Hosp Psychiat, Psychosis Res Unit, Aarhus, Denmark

[50] Aarhus Univ, Natl Ctr Register Based Res NCRR, Aarhus, Denmark

来源：

MOLECULAR PSYCHIATRY | 2025年

基金：

英国惠康基金;

关键词：

SPECTRUM DISORDER; MICROSTRUCTURE; OPTIMIZATION; EXPRESSION; RESOURCE; RISK;

D O I：

10.1038/s41380-025-02927-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.

引用

页数：11

共 79 条

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