PMID- 37407551
OWN - NLM
STAT- MEDLINE
DCOM- 20230707
LR  - 20230718
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Jul 6
TI  - A human leukocyte antigen imputation study uncovers possible genetic interplay 
      between gut inflammatory processes and autism spectrum disorders.
PG  - 244
LID - 10.1038/s41398-023-02550-y [doi]
LID - 244
AB  - Autism spectrum disorders (ASD) are neurodevelopmental conditions that are for 
      subsets of individuals, underpinned by dysregulated immune processes, including 
      inflammation, autoimmunity, and dysbiosis. Consequently, the major 
      histocompatibility complex (MHC)-hosted human leukocyte antigen (HLA) has been 
      implicated in ASD risk, although seldom investigated. By utilizing a GWAS 
      performed by the EU-AIMS consortium (LEAP cohort), we compared HLA and MHC 
      genetic variants, single nucleotide polymorphisms (SNP), and haplotypes in ASD 
      individuals, versus typically developing controls. We uncovered six SNPs, namely 
      rs9268528, rs9268542, rs9268556, rs14004, rs9268557, and rs8084 that crossed the 
      Bonferroni threshold, which form the underpinnings of 3 independent genetic 
      pathways/blocks that differentially associate with ASD. Block 1 (rs9268528-G, 
      rs9268542-G, rs9268556-C, and rs14004-A) afforded protection against ASD 
      development, whilst the two remaining blocks, namely rs9268557-T, and rs8084-A, 
      associated with heightened risk. rs8084 and rs14004 mapped to the HLA-DRA gene, 
      whilst the four other SNPs located in the BTNL2 locus. Different combinations 
      amongst BTNL2 SNPs and HLA amino acid variants or classical alleles were found 
      either to afford protection from or contribute to ASD risk, indicating a genetic 
      interplay between BTNL2 and HLA. Interestingly, the detected variants had 
      transcriptional and/or quantitative traits loci implications. As BTNL2 modulates 
      gastrointestinal homeostasis and the identified HLA alleles regulate the 
      gastrointestinal tract in celiac disease, it is proposed that the data on ASD 
      risk may be linked to genetically regulated gut inflammatory processes. These 
      findings might have implications for the prevention and treatment of ASD, via the 
      targeting of gut-related processes.
CI  - (c) 2023. The Author(s).
FAU - Lombardi, Laura
AU  - Lombardi L
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
AD  - Laboratoire Genomique, Bio-informatique et Chimie Moleculaire (EA7528), 
      Conservatoire National des Arts et Metiers, 292, rue Saint Martin, 75003, Paris, 
      France.
AD  - HESAM Universite, Paris, France.
FAU - Le Clerc, Sigrid
AU  - Le Clerc S
AD  - Laboratoire Genomique, Bio-informatique et Chimie Moleculaire (EA7528), 
      Conservatoire National des Arts et Metiers, 292, rue Saint Martin, 75003, Paris, 
      France.
AD  - HESAM Universite, Paris, France.
FAU - Wu, Ching-Lien
AU  - Wu CL
AUID- ORCID: 0000-0002-3254-6433
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
FAU - Bouassida, Jihene
AU  - Bouassida J
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
FAU - Boukouaci, Wahid
AU  - Boukouaci W
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
FAU - Sugusabesan, Sobika
AU  - Sugusabesan S
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
FAU - Richard, Jean-Romain
AU  - Richard JR
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
FAU - Lajnef, Mohamed
AU  - Lajnef M
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
FAU - Tison, Maxime
AU  - Tison M
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
AD  - Laboratoire Genomique, Bio-informatique et Chimie Moleculaire (EA7528), 
      Conservatoire National des Arts et Metiers, 292, rue Saint Martin, 75003, Paris, 
      France.
AD  - HESAM Universite, Paris, France.
FAU - Le Corvoisier, Philippe
AU  - Le Corvoisier P
AD  - Universite Paris Est Creteil, Inserm, Centre Investigation Clinique, CIC 1430, 
      Henri Mondor, Creteil, F94010, France.
FAU - Barau, Caroline
AU  - Barau C
AD  - Plateforme de Ressources Biologiques, HU Henri Mondor, Creteil, F94010, France.
FAU - Banaschewski, Tobias
AU  - Banaschewski T
AUID- ORCID: 0000-0003-4595-1144
AD  - Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental 
      Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Holt, Rosemary
AU  - Holt R
AD  - Autism Research Centre, Department of Psychiatry, University of Cambridge, 
      Cambridge, UK.
FAU - Durston, Sarah
AU  - Durston S
AD  - Education Center, University Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Persico, Antonio M
AU  - Persico AM
AD  - Child and Adolescent Neuropsychiatry Program at Modena University Hospital, & 
      Department of Biomedical, Metabolic and Neural Sciences, University of Modena and 
      Reggio Emilia, Modena, Italy.
FAU - Oakley, Bethany
AU  - Oakley B
AD  - Department of Forensic and Neurodevelopemental Science, Institute of Psychatry, 
      Psychology and Neuroscience, King's College London, London, United Kingdom.
FAU - Loth, Eva
AU  - Loth E
AUID- ORCID: 0000-0001-9458-9167
AD  - Department of Forensic and Neurodevelopemental Science, Institute of Psychatry, 
      Psychology and Neuroscience, King's College London, London, United Kingdom.
FAU - Buitelaar, Jan
AU  - Buitelaar J
AUID- ORCID: 0000-0001-8288-7757
AD  - Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and 
      Behaviour, Nijmegen, The Netherlands.
FAU - Murphy, Declan
AU  - Murphy D
AUID- ORCID: 0000-0002-6664-7451
AD  - Department of Forensic and Neurodevelopemental Science, Institute of Psychatry, 
      Psychology and Neuroscience, King's College London, London, United Kingdom.
FAU - Leboyer, Marion
AU  - Leboyer M
AUID- ORCID: 0000-0001-5473-3697
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France.
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, AP-HP, Hopital Henri Mondor, Departement Medico-Universitaire 
      de Psychiatrie et d'Addictologie (DMU IMPACT), Federation Hospitalo-Universitaire 
      de Medecine de Precision (FHU ADAPT) and Fondation FondaMental, Creteil, F-94010, 
      France.
FAU - Zagury, Jean-Francois
AU  - Zagury JF
AD  - Laboratoire Genomique, Bio-informatique et Chimie Moleculaire (EA7528), 
      Conservatoire National des Arts et Metiers, 292, rue Saint Martin, 75003, Paris, 
      France.
AD  - HESAM Universite, Paris, France.
FAU - Tamouza, Ryad
AU  - Tamouza R
AUID- ORCID: 0000-0003-3992-9565
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, F-94010, Creteil, France. tamouza.ryad@gmail.com.
AD  - Universite Paris Est Creteil, INSERM U955, IMRB, Laboratoire Neuro-Psychiatrie 
      translationnelle, AP-HP, Hopital Henri Mondor, Departement Medico-Universitaire 
      de Psychiatrie et d'Addictologie (DMU IMPACT), Federation Hospitalo-Universitaire 
      de Medecine de Precision (FHU ADAPT) and Fondation FondaMental, Creteil, F-94010, 
      France. tamouza.ryad@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230706
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (HLA Antigens)
RN  - 0 (BTNL2 protein, human)
RN  - 0 (Butyrophilins)
SB  - IM
MH  - Humans
MH  - *Autism Spectrum Disorder/genetics
MH  - HLA Antigens/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Haplotypes
MH  - Quantitative Trait Loci
MH  - Genetic Predisposition to Disease
MH  - Alleles
MH  - Butyrophilins/genetics
PMC - PMC10322870
COIS- The authors declare no competing interests.
EDAT- 2023/07/06 01:08
MHDA- 2023/07/07 06:42
PMCR- 2023/07/06
CRDT- 2023/07/05 23:14
PHST- 2023/06/02 00:00 [received]
PHST- 2023/06/27 00:00 [accepted]
PHST- 2023/06/24 00:00 [revised]
PHST- 2023/07/07 06:42 [medline]
PHST- 2023/07/06 01:08 [pubmed]
PHST- 2023/07/05 23:14 [entrez]
PHST- 2023/07/06 00:00 [pmc-release]
AID - 10.1038/s41398-023-02550-y [pii]
AID - 2550 [pii]
AID - 10.1038/s41398-023-02550-y [doi]
PST - epublish
SO  - Transl Psychiatry. 2023 Jul 6;13(1):244. doi: 10.1038/s41398-023-02550-y.