Abstract
Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
| Original language | English |
|---|---|
| Pages (from-to) | 936-949 |
| Number of pages | 14 |
| Journal | Nature Medicine |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2023 |
| Externally published | Yes |
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In: Nature Medicine, Vol. 29, No. 4, 04.2023, p. 936-949.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Interactions between the lipidome and genetic and environmental factors in autism
AU - Yap, Chloe X.
AU - Henders, Anjali K.
AU - Alvares, Gail A.
AU - Giles, Corey
AU - Huynh, Kevin
AU - Nguyen, Anh
AU - Wallace, Leanne
AU - McLaren, Tiana
AU - Yang, Yuanhao
AU - Hernandez, Leanna M.
AU - Gandal, Michael J.
AU - Hansell, Narelle K.
AU - Cleary, Dominique
AU - Grove, Rachel
AU - Hafekost, Claire
AU - Harun, Alexis
AU - Holdsworth, Helen
AU - Jellett, Rachel
AU - Khan, Feroza
AU - Lawson, Lauren P.
AU - Leslie, Jodie
AU - Levis Frenk, Mira
AU - Masi, Anne
AU - Mathew, Nisha E.
AU - Muniandy, Melanie
AU - Nothard, Michaela
AU - Miller, Jessica L.
AU - Nunn, Lorelle
AU - Strike, Lachlan T.
AU - Cadby, Gemma
AU - Moses, Eric K.
AU - Hung, Joseph
AU - Hui, Jennie
AU - Beilby, John
AU - de Zubicaray, Greig I.
AU - Thompson, Paul M.
AU - McMahon, Katie L.
AU - Wright, Margaret J.
AU - Visscher, Peter M.
AU - Dawson, Paul A.
AU - Dissanayake, Cheryl
AU - Eapen, Valsamma
AU - Heussler, Helen S.
AU - Whitehouse, Andrew J.O.
AU - Meikle, Peter J.
AU - Wray, Naomi R.
AU - Gratten, Jacob
AU - The Busselton Health Study Investigators
N1 - Funding Information: We thank all of the participants in the AAB and their families, without whom this study would not have been possible. The data used in this project were provided by the Cooperative Research Centre for Living with Autism (Autism CRC) with appropriate ethics approval. The Autism CRC is established and supported under the Australian Government’s Cooperative Research Centres Program and we acknowledge their financial support. We thank N. Silove and the Child Development Unit team at Sydney Children’s Hospital at Westmead, the staff at the KU Marcia Burgess Autism Specific Early Learning and Care Centre and KU Children’s Services, N. Sadka from the Olga Tennison Autism Research Centre at La Trobe University for her integral role in recruitment at the site in Victoria and A. Ravine and the pathology services at PathWest for contributions to collecting and processing blood samples in Perth. We thank F. Rose for assistance with the AAB. The QTAB Project thanks the twins and their families for their willingness to contribute to research and for giving their time so generously. Special thanks go to the many research assistants in the QTAB team and to the Human Studies Unit, Program in Complex Trait Genomics, Institute for Molecular Bioscience, The University of Queensland, for processing the QTAB samples and the Queensland Twin Registry Study. QTAB was facilitated through access to Twins Research Australia—a national resource supported by a Centres of Research Excellence grant (1078102) from the Australian National Health and Medical Research Council. We also acknowledge funding support from the Australian National Health and Medical Research Council (1103418 and 1127440 to J.G., 1078901 and 1173790 to N.R.W., 1113400 to N.R.W. and P.M.V., 1173896 to A.J.O.W. and 1078756 to M.J.W.), the Australian Research Council (FL180100072 to P.M.V.) and The University of Queensland (RTP Stipend and Tuition Fee Offset, Sam and Marion Frazer HDR Top-up Scholarship in Neurological Disease to C.X.Y.). This work was supported by Mater Research and the Mater Foundation and was carried out in part at the Translational Research Institute, which is supported by a grant from the Australian Government. Funding Information: We thank all of the participants in the AAB and their families, without whom this study would not have been possible. The data used in this project were provided by the Cooperative Research Centre for Living with Autism (Autism CRC) with appropriate ethics approval. The Autism CRC is established and supported under the Australian Government’s Cooperative Research Centres Program and we acknowledge their financial support. We thank N. Silove and the Child Development Unit team at Sydney Children’s Hospital at Westmead, the staff at the KU Marcia Burgess Autism Specific Early Learning and Care Centre and KU Children’s Services, N. Sadka from the Olga Tennison Autism Research Centre at La Trobe University for her integral role in recruitment at the site in Victoria and A. Ravine and the pathology services at PathWest for contributions to collecting and processing blood samples in Perth. We thank F. Rose for assistance with the AAB. The QTAB Project thanks the twins and their families for their willingness to contribute to research and for giving their time so generously. Special thanks go to the many research assistants in the QTAB team and to the Human Studies Unit, Program in Complex Trait Genomics, Institute for Molecular Bioscience, The University of Queensland, for processing the QTAB samples and the Queensland Twin Registry Study. QTAB was facilitated through access to Twins Research Australia—a national resource supported by a Centres of Research Excellence grant (1078102) from the Australian National Health and Medical Research Council. We also acknowledge funding support from the Australian National Health and Medical Research Council (1103418 and 1127440 to J.G., 1078901 and 1173790 to N.R.W., 1113400 to N.R.W. and P.M.V., 1173896 to A.J.O.W. and 1078756 to M.J.W.), the Australian Research Council (FL180100072 to P.M.V.) and The University of Queensland (RTP Stipend and Tuition Fee Offset, Sam and Marion Frazer HDR Top-up Scholarship in Neurological Disease to C.X.Y.). This work was supported by Mater Research and the Mater Foundation and was carried out in part at the Translational Research Institute, which is supported by a grant from the Australian Government. Funding Information: P.M.T. received a research grant from Biogen for research unrelated to this paper. The other authors declare no competing interests. Publisher Copyright: © 2023, The Author(s).
PY - 2023/4
Y1 - 2023/4
N2 - Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
AB - Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
UR - http://www.scopus.com/inward/record.url?scp=85152980511&partnerID=8YFLogxK
U2 - 10.1038/s41591-023-02271-1
DO - 10.1038/s41591-023-02271-1
M3 - Article
C2 - 37076741
AN - SCOPUS:85152980511
SN - 1078-8956
VL - 29
SP - 936
EP - 949
JO - Nature Medicine
JF - Nature Medicine
IS - 4
ER -