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1. Active juvenile systemic lupus erythematosus is associated with distinct NK cell transcriptional and phenotypic alterations

Author: Anna Radziszewska, Hannah Peckham, Nina M. de Gruijter, Restuadi Restuadi, Wing Han Wu, Elizabeth C. Jury, Elizabeth C. Rosser, and Coziana Ciurtin
Subjects: Medicine, Science
Abstract: Abstract While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.
Published: 2024
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2. Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Author: Restuadi Restuadi, Frederik J. Steyn, Edor Kabashi, Shyuan T. Ngo, Fei-Fei Cheng, Marta F. Nabais, Mike J. Thompson, Ting Qi, Yang Wu, Anjali K. Henders, Leanne Wallace, Chris R. Bye, Bradley J. Turner, Laura Ziser, Susan Mathers, Pamela A. McCombe, Merrilee Needham, David Schultz, Matthew C. Kiernan, Wouter van Rheenen, Leonard H. van den Berg, Jan H. Veldink, Roel Ophoff, Alexander Gusev, Noah Zaitlen, Allan F. McRae, Robert D. Henderson, Naomi R. Wray, Jean Giacomotto, and Fleur C. Garton
Subjects: Motor neurone disease, MND, Genome-wide association study, Computational biology, Zebrafish, Neurodegenerative diseases, Medicine, Genetics, QH426-470
Abstract: Abstract Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (N cases = 20,806, N controls = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray N total = 942, protein N total = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R 2 = 0.042, B effect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all
Published: 2022
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3. Phylodynamics of Highly Pathogenic Avian Influenza A(H5N1) Virus Circulating in Indonesian Poultry

Author: Desniwaty Karo-karo, Rogier Bodewes, Restuadi Restuadi, Alex Bossers, Agustiningsih Agustiningsih, Jan Arend Stegeman, Guus Koch, and David Handojo Muljono
Subjects: HPAI, H5N1, Indonesia, phylodynamic, Bayesian evolutionary analysis, Microbiology, QR1-502
Abstract: After its first detection in 1996, the highly pathogenic avian influenza A(H5Nx) virus has spread extensively worldwide. HPAIv A(H5N1) was first detected in Indonesia in 2003 and has been endemic in poultry in this country ever since. However, Indonesia has limited information related to the phylodynamics of HPAIv A(H5N1) in poultry. The present study aimed to increase the understanding of the evolution and temporal dynamics of HPAIv H5N1 in Indonesian poultry between 2003 and 2016. To this end, HPAIv A(H5N1) hemagglutinin sequences of viruses collected from 2003 to 2016 were analyzed using Bayesian evolutionary analysis sampling trees. Results indicated that the common ancestor of Indonesian poultry HPAIv H5N1 arose approximately five years after the common ancestor worldwide of HPAI A(H5Nx). In addition, this study indicated that only two introductions of HPAIv A(H5N1) occurred, after which these viruses continued to evolve due to extensive spread among poultry. Furthermore, this study revealed the divergence of H5N1 clade 2.3.2.1c from H5N1 clade 2.3.2.1b. Both clades 2.3.2.1c and 2.3.2.1b share a common ancestor, clade 1, suggesting that clade 2.3.2.1 originated and diverged from China and other Asian countries. Since there was limited sequence and surveillance data for the HPAIv A(H5N1) from wild birds in Indonesia, the exact role of wild birds in the spread of HPAIv in Indonesia is currently unknown. The evolutionary dynamics of the Indonesian HPAIv A(H5N1) highlight the importance of continuing and improved genomic surveillance and adequate control measures in the different regions of both the poultry and wild birds. Spatial genomic surveillance is useful to take adequate control measures. Therefore, it will help to prevent the future evolution of HPAI A(H5N1) and pandemic threats.
Published: 2022
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4. Genetic regulation of methylation in human endometrium and blood and gene targets for reproductive diseases

Author: Sally Mortlock, Restuadi Restuadi, Rupert Levien, Jane E. Girling, Sarah J. Holdsworth-Carson, Martin Healey, Zhihong Zhu, Ting Qi, Yang Wu, Samuel W. Lukowski, Peter A. W. Rogers, Jian Yang, Allan F. McRae, Jenny N. Fung, and Grant W. Montgomery
Subjects: DNA methylation, DNA methylation quantitative trait loci (mQTL), Endometrium, Blood, Menstrual cycle, Endometriosis, Medicine, Genetics, QH426-470
Abstract: Abstract Background Major challenges in understanding the functional consequences of genetic risk factors for human disease are which tissues and cell types are affected and the limited availability of suitable tissue. The aim of this study was to evaluate tissue-specific genotype-epigenetic characteristics in DNA samples from both endometrium and blood collected from women at different stages of the menstrual cycle and relate results to genetic risk factors for reproductive traits and diseases. Results We analysed DNA methylation (DNAm) data from endometrium and blood samples from 66 European women. Methylation profiles were compared between stages of the menstrual cycle, and changes in methylation overlaid with changes in transcription and genotypes. We observed large changes in methylation (27,262 DNAm probes) across the menstrual cycle in endometrium that were not observed in blood. Individual genotype data was tested for association with methylation at 443,016 and 443,101 DNAm probes in endometrium and blood respectively to identify methylation quantitative trait loci (mQTLs). A total of 4546 sentinel cis-mQTLs (P
Published: 2019
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5. Active juvenile systemic lupus erythematosus is associated with distinct NK cell transcriptional and phenotypic alterations

Author: Radziszewska, Anna, Peckham, Hannah, de Gruijter, Nina M., Restuadi, Restuadi, Wu, Wing Han, Jury, Elizabeth C., Rosser, Elizabeth C., and Ciurtin, Coziana
Published: 2024
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6. Evolutionary study and phylodynamic pattern of human influenza A/H3N2 virus in Indonesia from 2008 to 2010.

Author: Agustiningsih Agustiningsih, Hidayat Trimarsanto, Restuadi Restuadi, I Made Artika, Margaret Hellard, and David Handojo Muljono
Subjects: Medicine, Science
Abstract: Influenza viruses are by nature unstable with high levels of mutations. The sequential accumulation of mutations in the surface glycoproteins allows the virus to evade the neutralizing antibodies. The consideration of the tropics as the influenza reservoir where viral genetic and antigenic diversity are continually generated and reintroduced into temperate countries makes the study of influenza virus evolution in Indonesia essential. A total of 100 complete coding sequences (CDS) of Hemagglutinin (HA) and Neuraminidase (NA) genes of H3N2 virus were obtained from archived samples of Influenza-Like Illness (ILI) surveillance collected from 2008 to 2010. Our evolutionary and phylogenetic analyses provide insight into the dynamic changes of Indonesian H3N2 virus from 2008 to 2010. Obvious antigenic drift with typical 'ladder-like' phylogeny was observed with multiple lineages found in each year, suggesting co-circulation of H3N2 strains at different time periods. The mutational pattern of the Indonesian H3N2 virus was not geographically related as relatively low levels of mutations with similar pattern of relative genetic diversity were observed in various geographical origins. This study reaffirms that the existence of a particular lineage is most likely the result of adaptation or competitive exclusion among different host populations and combination of stochastic ecological factors, rather than its geographical origin alone.
Published: 2018
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7. Isolation and complete genome analysis of neurotropic dengue virus serotype 3 from the cerebrospinal fluid of an encephalitis patient.

Author: Rama Dhenni, Mulya Rahma Karyanti, Nina Dwi Putri, Benediktus Yohan, Frilasita A Yudhaputri, Chairin Nisa Ma'roef, Araniy Fadhilah, Aditya Perkasa, Restuadi Restuadi, Hidayat Trimarsanto, Irawan Mangunatmadja, Jeremy P Ledermann, Ronald Rosenberg, Ann M Powers, Khin Saw Aye Myint, and R Tedjo Sasmono
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: Although neurological manifestations associated with dengue viruses (DENV) infection have been reported, there is very limited information on the genetic characteristics of neurotropic DENV. Here we describe the isolation and complete genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing was employed to deduce the complete genome of the neurotropic DENV-3 isolate. Based on complete genome analysis, two unique and nine uncommon amino acid changes in the protein coding region were observed in the virus. A phylogenetic tree and molecular clock analysis revealed that the neurotropic virus was a member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor with other isolates from Jakarta around 1998. This is the first report of neurotropic DENV-3 complete genome analysis, providing detailed information on the genetic characteristics of this virus.
Published: 2018
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8. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick AA, Bakker, Mark K, van Vugt, Joke JFA, Hop, Paul J, Zwamborn, Ramona AJ, de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B, Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M, Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs HP, van Eijk, Kristel R, Kooyman, Maarten, Byrne, Ross P, Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N, Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J, Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H, Bell, Shaughn, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S, Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A, Ross, Jay P, Ludolph, Albert C, Weishaupt, Jochen H, Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine AM, Saker-Delye, Safa, Wood, Nicholas W, Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, and Kraft, Julia
Subjects: Human Genome, Neurodegenerative, Clinical Research, Rare Diseases, Prevention, ALS, Neurosciences, Genetics, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Amyotrophic Lateral Sclerosis, Brain, Cholesterol, Disease Progression, Female, Genome-Wide Association Study, Glutamine, Humans, Male, Mendelian Randomization Analysis, Microsatellite Repeats, Mutation, Neurodegenerative Diseases, Neurons, Quantitative Trait Loci, RNA-Seq, Risk Factors, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, SLAP Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021

9. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Author: Wienke, Judith, Visser, Lindy L., Kholosy, Waleed M., Keller, Kaylee M., Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R., Matser, Yvette A.H., Tas, Michelle L., Langenberg, Karin P.S., Lijnzaad, Philip, Borst, Anne L., Zappa, Elisa, Bergsma, Francisca J., Strijker, Josephine G.M., Verhoeven, Bronte M., Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M., Holstege, Frank C.P., Gray, Juliet C., Tytgat, Godelieve A.M., Scheijde-Vermeulen, Marijn A., Wijnen, Marc H.W.A., Dierselhuis, Miranda P., Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J.R., Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R., Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N., Margaritis, Thanasis, van Noesel, Max M., and Molenaar, Jan J.
Published: 2024
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10. Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia

Author: Priliani, Lidwina, Prado, Elizabeth L, Restuadi, Restuadi, Waturangi, Diana E, Shankar, Anuraj H, and Malik, Safarina G
Subjects: Reproductive Medicine, Biomedical and Clinical Sciences, Pediatric, Prevention, Conditions Affecting the Embryonic and Fetal Periods, Clinical Research, Clinical Trials and Supportive Activities, Nutrition, Perinatal Period - Conditions Originating in Perinatal Period, Reproductive health and childbirth, Good Health and Well Being, Adult, DNA Copy Number Variations, DNA, Mitochondrial, Dietary Supplements, Female, Humans, Indonesia, Micronutrients, Oxidative Stress, Pregnancy, Randomized Controlled Trials as Topic, Young Adult, supplementation, multiple micronutrients, iron and folic acid, pregnancy, mitochondrial DNA copy number, mtDNA-CN, oxidative stress, Animal Production, Food Sciences, Nutrition and Dietetics, Nutrition & Dietetics, Animal production, Food sciences, Nutrition and dietetics
Abstract: BackgroundThe Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood.ObjectiveThe aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN).MethodsWe used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models.ResultsIn both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P
Published: 2019

11. Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

Author: Restuadi, Restuadi, Garton, Fleur C., Benyamin, Beben, Lin, Tian, Williams, Kelly L., Vinkhuyzen, Anna, van Rheenen, Wouter, Zhu, Zhihong, Laing, Nigel G., Mather, Karen A., Sachdev, Perminder S., Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Henders, Anjali K., Visscher, Peter M., Needham, Merrilee, Mathers, Susan, Nicholson, Garth, Rowe, Dominic B., Henderson, Robert D., McCombe, Pamela A., Pamphlett, Roger, Blair, Ian P., Wray, Naomi R., and McRae, Allan F.
Published: 2022
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12. Autism-related dietary preferences mediate autism-gut microbiome associations

Author: Yap, Chloe X., Henders, Anjali K., Alvares, Gail A., Wood, David L.A., Krause, Lutz, Tyson, Gene W., Restuadi, Restuadi, Wallace, Leanne, McLaren, Tiana, Hansell, Narelle K., Cleary, Dominique, Grove, Rachel, Hafekost, Claire, Harun, Alexis, Holdsworth, Helen, Jellett, Rachel, Khan, Feroza, Lawson, Lauren P., Leslie, Jodie, Frenk, Mira Levis, Masi, Anne, Mathew, Nisha E., Muniandy, Melanie, Nothard, Michaela, Miller, Jessica L., Nunn, Lorelle, Holtmann, Gerald, Strike, Lachlan T., de Zubicaray, Greig I., Thompson, Paul M., McMahon, Katie L., Wright, Margaret J., Visscher, Peter M., Dawson, Paul A., Dissanayake, Cheryl, Eapen, Valsamma, Heussler, Helen S., McRae, Allan F., Whitehouse, Andrew J.O., Wray, Naomi R., and Gratten, Jacob
Published: 2021
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13. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Author: Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Pharmaceutics, Biomolecular Mass Spectrometry and Proteomics, Pharmaceutics, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, Molenaar, Jan J, Afd Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Afd Pharmaceutics, Biomolecular Mass Spectrometry and Proteomics, Pharmaceutics, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, and Molenaar, Jan J
Published: 2024

14. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Author: CTI Nierkens, Cancer, Infection & Immunity, CTI Research, Pathologie Pathologen staf, Onderzoek Beeld, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, Molenaar, Jan J, CTI Nierkens, Cancer, Infection & Immunity, CTI Research, Pathologie Pathologen staf, Onderzoek Beeld, Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, Keller, Kaylee M, Barisa, Marta, Poon, Evon, Munnings-Tomes, Sophie, Himsworth, Courtney, Calton, Elizabeth, Rodriguez, Ana, Bernardi, Ronald, van den Ham, Femke, van Hooff, Sander R, Matser, Yvette A H, Tas, Michelle L, Langenberg, Karin P S, Lijnzaad, Philip, Borst, Anne L, Zappa, Elisa, Bergsma, Francisca J, Strijker, Josephine G M, Verhoeven, Bronte M, Mei, Shenglin, Kramdi, Amira, Restuadi, Restuadi, Sanchez-Bernabeu, Alvaro, Cornel, Annelisa M, Holstege, Frank C P, Gray, Juliet C, Tytgat, Godelieve A M, Scheijde-Vermeulen, Marijn A, Wijnen, Marc H W A, Dierselhuis, Miranda P, Straathof, Karin, Behjati, Sam, Wu, Wei, Heck, Albert J R, Koster, Jan, Nierkens, Stefan, Janoueix-Lerosey, Isabelle, de Krijger, Ronald R, Baryawno, Ninib, Chesler, Louis, Anderson, John, Caron, Hubert N, Margaritis, Thanasis, van Noesel, Max M, and Molenaar, Jan J
Published: 2024

15. Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease patient-derived tissue.

Author: Jevans, Benjamin, Cooper, Fay, Fatieieva, Yuliia, Gogolou, Antigoni, Yi-Ning Kang, Restuadi, Restuadi, Moulding, Dale, Berghe, Pieter Vanden, Adameyko, Igor, Thapar, Nikhil, Andrews, Peter W., De Coppi, Paolo, Tsakiridis, Anestis, and McCann, Conor J.
Subjects: HUMAN embryonic stem cells, ENTERIC nervous system, HIRSCHSPRUNG'S disease, STEM cell culture, GASTROINTESTINAL system
Published: 2024
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16. Autism-related dietary preferences mediate autism-gut microbiome associations

Author: Yap, Chloe X., primary, Henders, Anjali K., additional, Alvares, Gail A., additional, Wood, David L.A., additional, Krause, Lutz, additional, Tyson, Gene W., additional, Restuadi, Restuadi, additional, Wallace, Leanne, additional, McLaren, Tiana, additional, Hansell, Narelle K., additional, Cleary, Dominique, additional, Grove, Rachel, additional, Hafekost, Claire, additional, Harun, Alexis, additional, Holdsworth, Helen, additional, Jellett, Rachel, additional, Khan, Feroza, additional, Lawson, Lauren P., additional, Leslie, Jodie, additional, Frenk, Mira Levis, additional, Masi, Anne, additional, Mathew, Nisha E., additional, Muniandy, Melanie, additional, Nothard, Michaela, additional, Miller, Jessica L., additional, Nunn, Lorelle, additional, Holtmann, Gerald, additional, Strike, Lachlan T., additional, de Zubicaray, Greig I., additional, Thompson, Paul M., additional, McMahon, Katie L., additional, Wright, Margaret J., additional, Visscher, Peter M., additional, Dawson, Paul A., additional, Dissanayake, Cheryl, additional, Eapen, Valsamma, additional, Heussler, Helen S., additional, McRae, Allan F., additional, Whitehouse, Andrew J.O., additional, Wray, Naomi R., additional, and Gratten, Jacob, additional
Published: 2024
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17. Human enteric nervous system progenitor transplantation restores functional responses in Hirschsprung Disease patient-derived tissue

Author: Jevans, Benjamin, primary, Cooper, Fay, additional, Fatieieva, Yuliia, additional, Gogolou, Antigoni, additional, Kang, Yi-Ning, additional, Restuadi, Restuadi, additional, Vanden Berghe, Pieter, additional, Adameyko, Igor, additional, Thapar, Nikhil, additional, Andrews, Peter W, additional, De Coppi, Paolo, additional, Tsakiridis, Anestis, additional, and McCann, Conor J, additional
Published: 2023
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18. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Hübner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Jr., Robert H., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.
Published: 2022
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19. Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Author: Nabais, Marta F., Lin, Tian, Benyamin, Beben, Williams, Kelly L., Garton, Fleur C., Vinkhuyzen, Anna A. E., Zhang, Futao, Vallerga, Costanza L., Restuadi, Restuadi, Freydenzon, Anna, Zwamborn, Ramona A. J., Hop, Paul J., Robinson, Matthew R., Gratten, Jacob, Visscher, Peter M., Hannon, Eilis, Mill, Jonathan, Brown, Matthew A., Laing, Nigel G., Mather, Karen A., Sachdev, Perminder S., Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Henders, Anjali K., Needham, Merrilee, Veldink, Jan H., Mathers, Susan, Nicholson, Garth, Rowe, Dominic B., Henderson, Robert D., McCombe, Pamela A., Pamphlett, Roger, Yang, Jian, Blair, Ian P., McRae, Allan F., and Wray, Naomi R.
Published: 2020
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20. Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis

Author: Meredyth G Ll Wilkinson, Dale Moulding, Thomas C R McDonnell, Michael Orford, Chris Wincup, Joanna Y J Ting, Georg W Otto, Restuadi Restuadi, Daniel Kelberman, Charalampia Papadopoulou, Sergi Castellano, Simon Eaton, Claire T Deakin, Elizabeth C Rosser, and Lucy R Wedderburn
Subjects: Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract: ObjectivesTo define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM).MethodsRNA-sequencing was performed on CD4+, CD8+, CD14+and CD19+cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by13C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot. Healthy-control PBMC and JDM pretreatment PBMC were cultured with IFN-α, oxmtDNA, cGAS-inhibitor, TLR-9 antagonist and/orn-acetyl cysteine (NAC). IFN-stimulated gene (ISGs) expression was measured by qPCR. Total numbers of patient and controls for functional experiments, JDM n=82, total CHC n=35.ResultsDysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes. Altered mitochondrial-associated gene expression was paralleled by altered mitochondrial biology, including ‘megamitochondria’, cellular metabolism and a decrease in gene expression of superoxide dismutase (SOD)1. This was associated with enhanced production of oxidised mitochondrial (oxmt)DNA. OxmtDNA induced ISG expression in healthy PBMC, which was blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways. Complementary experiments showed that, under in vitro experimental conditions, targeting these pathways via the antioxidant drug NAC, TLR9 antagonist and to a lesser extent cGAS-inhibitor, suppressed ISG expression in pretreatment JDM PBMC.ConclusionsThese results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression. Targeting this pathway has therapeutical potential in JDM and other IFN type 1-driven autoimmune diseases.
Published: 2022
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21. Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1.

Author: Restuadi, Restuadi, Restuadi, Restuadi, Steyn, Frederik J, Kabashi, Edor, Ngo, Shyuan T, Cheng, Fei-Fei, Nabais, Marta F, Thompson, Mike J, Qi, Ting, Wu, Yang, Henders, Anjali K, Wallace, Leanne, Bye, Chris R, Turner, Bradley J, Ziser, Laura, Mathers, Susan, McCombe, Pamela A, Needham, Merrilee, Schultz, David, Kiernan, Matthew C, van Rheenen, Wouter, van den Berg, Leonard H, Veldink, Jan H, Ophoff, Roel, Gusev, Alexander, Zaitlen, Noah, McRae, Allan F, Henderson, Robert D, Wray, Naomi R, Giacomotto, Jean, Garton, Fleur C, Restuadi, Restuadi, Restuadi, Restuadi, Steyn, Frederik J, Kabashi, Edor, Ngo, Shyuan T, Cheng, Fei-Fei, Nabais, Marta F, Thompson, Mike J, Qi, Ting, Wu, Yang, Henders, Anjali K, Wallace, Leanne, Bye, Chris R, Turner, Bradley J, Ziser, Laura, Mathers, Susan, McCombe, Pamela A, Needham, Merrilee, Schultz, David, Kiernan, Matthew C, van Rheenen, Wouter, van den Berg, Leonard H, Veldink, Jan H, Ophoff, Roel, Gusev, Alexander, Zaitlen, Noah, McRae, Allan F, Henderson, Robert D, Wray, Naomi R, Giacomotto, Jean, and Garton, Fleur C
Abstract: BackgroundAmyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this.MethodsThe Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with 'omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO).ResultsSMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10-6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10-3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s
Published: 2022

22. Mapping and differential expression analysis from short-read RNA-Seq data in model organisms.

Author: Qiong-Yi Zhao, Jacob Gratten, Restuadi Restuadi, and Xuan Li
Published: 2016
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23. Genetic regulation of methylation in human endometrium and blood and gene targets for reproductive diseases

Author: Mortlock, Sally, Restuadi, Restuadi, Levien, Rupert, Girling, Jane E., Holdsworth-Carson, Sarah J., Healey, Martin, Zhu, Zhihong, Qi, Ting, Wu, Yang, Lukowski, Samuel W., Rogers, Peter A. W., Yang, Jian, McRae, Allan F., Fung, Jenny N., and Montgomery, Grant W.
Published: 2019
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24. Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

Author: Anjali K. Henders, Pamela A. McCombe, Nigel G. Laing, Perminder S. Sachdev, Allan F. McRae, Garth A. Nicholson, Fleur C. Garton, Beben Benyamin, Wouter van Rheenen, Anna A. E. Vinkhuyzen, Frederik J. Steyn, Restuadi Restuadi, Leanne Wallace, Dominic B. Rowe, Susan Mathers, Robert D. Henderson, Zhihong Zhu, Shyuan T. Ngo, Kelly L. Williams, Tian Lin, Karen A. Mather, Ian P. Blair, Merrilee Needham, Naomi R. Wray, Roger Pamphlett, Peter M. Visscher, Restuadi, Restuadi, Garton, Fleur C, Benyamin, Beben, Lin, Tian, and McRae, Allan F
Subjects: Oncology, medicine.medical_specialty, Genome-wide association study, Disease, Logistic regression, Polymorphism, Single Nucleotide, Genetic correlation, Article, 03 medical and health sciences, Cognition, Risk Factors, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Effects of sleep deprivation on cognitive performance, Amyotrophic lateral sclerosis, Genetics (clinical), 0303 health sciences, business.industry, Amyotrophic Lateral Sclerosis, 030305 genetics & heredity, Australia, Neurodegenerative Diseases, medicine.disease, Schizophrenia, Cohort, business, Genome-Wide Association Study
Abstract: Amyotrophic Lateral Sclerosis (ALS) is recognised to be a complex neurodegenerative disease involving both genetic and non-genetic risk factors. The underlying causes and risk factors for the majority of cases remain unknown; however, ever-larger genetic data studies and methodologies promise an enhanced understanding. Recent analyses using published summary statistics from the largest ALS genome-wide association study (GWAS) (20,806 ALS cases and 59,804 healthy controls) identified that schizophrenia (SCZ), cognitive performance (CP) and educational attainment (EA) related traits were genetically correlated with ALS. To provide additional evidence for these correlations, we built single and multi-trait genetic predictors using GWAS summary statistics for ALS and these traits, (SCZ, CP, EA) in an independent Australian cohort (846 ALS cases and 665 healthy controls). We compared methods for generating the risk predictors and found that the combination of traits improved the prediction (Nagelkerke-R-2) of the case-control logistic regression. The combination of ALS, SCZ, CP, and EA, using the SBayesR predictor method gave the highest prediction (Nagelkerke-R-2) of 0.027 (P value = 4.6 x 10(-8)), with the odds-ratio for estimated disease risk between the highest and lowest deciles of individuals being 3.15 (95% CI 1.96-5.05). These results support the genetic correlation between ALS, SCZ, CP and EA providing a better understanding of the complexity of ALS. Refereed/Peer-reviewed
Published: 2021
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25. Phylodynamics of Highly Pathogenic Avian Influenza A(H5N1) Virus Circulating in Indonesian Poultry

Author: Karo-Karo, Desniwaty, Bodewes, Rogier, Restuadi, Restuadi, Bossers, Alex, Agustiningsih, Agustiningsih, Stegeman, Jan Arend, Koch, Guus, Muljono, David Handojo, IRAS OH Epidemiology Microbial Agents, FAH veterinaire epidemiologie, IRAS OH Epidemiology Microbial Agents, and FAH veterinaire epidemiologie
Subjects: Influenza A Virus, H5N1 Subtype, Bayes Theorem, Bayesian evolutionary analysis, H5N1, HPAI, Poultry, Virology & Molecular Biology, Virologie & Moleculaire Biologie, Birds, Indonesia, phylodynamic, Infectious Diseases, Hemagglutinins, Virology, Influenza in Birds, Animals, Phylogeny, Poultry Diseases
Abstract: After its first detection in 1996, the highly pathogenic avian influenza A(H5Nx) virus has spread extensively worldwide. HPAIv A(H5N1) was first detected in Indonesia in 2003 and has been endemic in poultry in this country ever since. However, Indonesia has limited information related to the phylodynamics of HPAIv A(H5N1) in poultry. The present study aimed to increase the understanding of the evolution and temporal dynamics of HPAIv H5N1 in Indonesian poultry between 2003 and 2016. To this end, HPAIv A(H5N1) hemagglutinin sequences of viruses collected from 2003 to 2016 were analyzed using Bayesian evolutionary analysis sampling trees. Results indicated that the common ancestor of Indonesian poultry HPAIv H5N1 arose approximately five years after the common ancestor worldwide of HPAI A(H5Nx). In addition, this study indicated that only two introductions of HPAIv A(H5N1) occurred, after which these viruses continued to evolve due to extensive spread among poultry. Furthermore, this study revealed the divergence of H5N1 clade 2.3.2.1c from H5N1 clade 2.3.2.1b. Both clades 2.3.2.1c and 2.3.2.1b share a common ancestor, clade 1, suggesting that clade 2.3.2.1 originated and diverged from China and other Asian countries. Since there was limited sequence and surveillance data for the HPAIv A(H5N1) from wild birds in Indonesia, the exact role of wild birds in the spread of HPAIv in Indonesia is currently unknown. The evolutionary dynamics of the Indonesian HPAIv A(H5N1) highlight the importance of continuing and improved genomic surveillance and adequate control measures in the different regions of both the poultry and wild birds. Spatial genomic surveillance is useful to take adequate control measures. Therefore, it will help to prevent the future evolution of HPAI A(H5N1) and pandemic threats.
Published: 2022
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26. Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis

Author: Wilkinson, Meredyth G Ll, primary, Moulding, Dale, additional, McDonnell, Thomas C R, additional, Orford, Michael, additional, Wincup, Chris, additional, Ting, Joanna Y J, additional, Otto, Georg W, additional, Restuadi, Restuadi, additional, Kelberman, Daniel, additional, Papadopoulou, Charalampia, additional, Castellano, Sergi, additional, Eaton, Simon, additional, Deakin, Claire T, additional, Rosser, Elizabeth C, additional, and Wedderburn, Lucy R, additional
Published: 2022
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27. Mapping and differential expression analysis from short-read RNA-Seq data in model organisms

Author: Zhao, Qiong-Yi, Gratten, Jacob, Restuadi, Restuadi, and Li, Xuan
Published: 2016
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28. Phylodynamics of Highly Pathogenic Avian Influenza A(H5N1) Virus Circulating in Indonesian Poultry

Author: IRAS OH Epidemiology Microbial Agents, FAH veterinaire epidemiologie, Karo-Karo, Desniwaty, Bodewes, Rogier, Restuadi, Restuadi, Bossers, Alex, Agustiningsih, Agustiningsih, Stegeman, Jan Arend, Koch, Guus, Muljono, David Handojo, IRAS OH Epidemiology Microbial Agents, FAH veterinaire epidemiologie, Karo-Karo, Desniwaty, Bodewes, Rogier, Restuadi, Restuadi, Bossers, Alex, Agustiningsih, Agustiningsih, Stegeman, Jan Arend, Koch, Guus, and Muljono, David Handojo
Published: 2022

29. Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Author: Neurologen, Projectafdeling ALS, Brain, Regenerative Medicine and Stem Cells, Genetic Risks, Neuromuscular Disorders, Restuadi, Restuadi, Steyn, Frederik J, Kabashi, Edor, Ngo, Shyuan T, Cheng, Fei-Fei, Nabais, Marta F, Thompson, Mike J, Qi, Ting, Wu, Yang, Henders, Anjali K, Wallace, Leanne, Bye, Chris R, Turner, Bradley J, Ziser, Laura, Mathers, Susan, McCombe, Pamela A, Needham, Merrilee, Schultz, David, Kiernan, Matthew C, van Rheenen, Wouter, van den Berg, Leonard H, Veldink, Jan H, Ophoff, Roel, Gusev, Alexander, Zaitlen, Noah, McRae, Allan F, Henderson, Robert D, Wray, Naomi R, Giacomotto, Jean, Garton, Fleur C, Neurologen, Projectafdeling ALS, Brain, Regenerative Medicine and Stem Cells, Genetic Risks, Neuromuscular Disorders, Restuadi, Restuadi, Steyn, Frederik J, Kabashi, Edor, Ngo, Shyuan T, Cheng, Fei-Fei, Nabais, Marta F, Thompson, Mike J, Qi, Ting, Wu, Yang, Henders, Anjali K, Wallace, Leanne, Bye, Chris R, Turner, Bradley J, Ziser, Laura, Mathers, Susan, McCombe, Pamela A, Needham, Merrilee, Schultz, David, Kiernan, Matthew C, van Rheenen, Wouter, van den Berg, Leonard H, Veldink, Jan H, Ophoff, Roel, Gusev, Alexander, Zaitlen, Noah, McRae, Allan F, Henderson, Robert D, Wray, Naomi R, Giacomotto, Jean, and Garton, Fleur C
Published: 2022

30. Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis.

Author: L. I. Wilkinson, Meredyth G., Moulding, Dale, McDonnell, Thomas C. R., Orford, Michael, Wincup, Chris, Ting, Joanna Y. J., Otto, Georg W., Restuadi, Restuadi, Kelberman, Daniel, Papadopoulou, Charalampia, Castellano, Sergi, Eaton, Simon, Deakin, Claire T., Rosser, Elizabeth C., and Wedderburn, Lucy R.
Published: 2023
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31. Progression and survival of patients with motor neuron disease relative to their fecal microbiota

Author: Robert D. Henderson, Allan F McCrae, Frederik J. Steyn, Restuadi Restuadi, Shyuan T. Ngo, Ruben P A van Eijk, Pamela A. McCombe, Naomi R. Wray, and Fleur C. Garton
Subjects: biology, Firmicutes, Microbiota, Amyotrophic Lateral Sclerosis, Bacteroidetes, Physiology, Disease, Gut flora, biology.organism_classification, medicine.disease, Feces, 03 medical and health sciences, 0302 clinical medicine, Neurology, Metagenomics, RNA, Ribosomal, 16S, medicine, Humans, Neurology (clinical), Microbiome, Motor Neuron Disease, Amyotrophic lateral sclerosis, 030217 neurology & neurosurgery
Abstract: Gut microbiota studies have been well-investigated for neurodegenerative diseases such as Alzheimer's and Parkinson's disease, however, fewer studies have comprehensively examined the gut microbiome in Motor Neuron Disease (MND), with none examining its impact on disease prognosis. Here, we investigate MND prognosis and the fecal microbiota, using 16S rRNA case-control data from 100 individuals with extensive medical histories and metabolic measurements. We contrast the composition and diversity of fecal microbiome signatures from 49 MND and 51 healthy controls by combining current gold-standard 16S microbiome pipelines. Using stringent quality control thresholds, we conducted qualitative assessment approaches including; direct comparison of taxa, PICRUSt2 predicted metagenomics, Shannon and Chao1-index and Firmicutes/Bacteroidetes ratio. We show that the fecal microbiome of patients with MND is not significantly different from that of healthy controls that were matched by age, sex, and BMI, however there are distinct differences in Beta-diversity in some patients with MND. Weight, BMI, and metabolic and clinical features of disease in patients with MND were not related to the composition of their fecal microbiome, however, we observe a greater risk for earlier death in patients with MND with increased richness and diversity of the microbiome, and in those with greater Firmicutes to Bacteroidetes ratio. This was independent of anthropometric, metabolic, or clinical features of disease, and warrants support for further gut microbiota studies in MND. Given the disease heterogeneity in MND, and complexity of the gut microbiota, large studies are necessary to determine the detailed role of the gut microbiota and MND prognosis.
Published: 2020
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32. Tissue specific regulation of transcription in endometrium and association with disease

Author: Greg Gibson, Jian Yang, Peter Rogers, Grant W. Montgomery, Samuel W. Lukowski, Fei Yang, Wan Tinn Teh, Martin Healey, Sally Mortlock, Sarah J Holdsworth-Carson, Restuadi Restuadi, Jenny N. Fung, Brett McKinnon, Raden I Kendarsari, Jane E. Girling, and Ting Qi
Subjects: endometriosis, Quantitative Trait Loci, RNA-sequencing, Endometriosis, Genome-wide association study, Biology, Quantitative trait locus, Bioinformatics, tissue specific, genetic regulation, Endometrium, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Genotype, medicine, Humans, Gene, Menstrual Cycle, 030304 developmental biology, Regulation of gene expression, Reproductive Biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, Rehabilitation, Obstetrics and Gynecology, medicine.disease, Reproductive Medicine, expression quantitative trait loci (eQTL), Expression quantitative trait loci, gene expression, Female, Original Article, Genome-Wide Association Study
Abstract: STUDY QUESTION Are genetic effects on endometrial gene expression tissue specific and/or associated with reproductive traits and diseases? SUMMARY ANSWER Analyses of RNA-sequence data and individual genotype data from the endometrium identified novel and disease associated, genetic mechanisms regulating gene expression in the endometrium and showed evidence that these mechanisms are shared across biologically similar tissues. WHAT IS KNOWN ALREADY The endometrium is a complex tissue vital for female reproduction and is a hypothesized source of cells initiating endometriosis. Understanding genetic regulation specific to, and shared between, tissue types can aid the identification of genes involved in complex genetic diseases. STUDY DESIGN, SIZE, DURATION RNA-sequence and genotype data from 206 individuals was analysed and results were compared with large publicly available datasets. PARTICIPANTS/MATERIALS, SETTING, METHODS RNA-sequencing and genotype data from 206 endometrial samples was used to identify the influence of genetic variants on gene expression, via expression quantitative trait loci (eQTL) analysis and to compare these endometrial eQTLs with those in other tissues. To investigate the association between endometrial gene expression regulation and reproductive traits and diseases, we conducted a tissue enrichment analysis, transcriptome-wide association study (TWAS) and summary data-based Mendelian randomisation (SMR) analyses. Transcriptomic data was used to test differential gene expression between women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE A tissue enrichment analysis with endometriosis genome-wide association study summary statistics showed that genes surrounding endometriosis risk loci were significantly enriched in reproductive tissues. A total of 444 sentinel cis-eQTLs (P LARGE SCALE DATA The eQTL dataset generated in this study is available at http://reproductivegenomics.com.au/shiny/endo_eqtl_rna/. Additional datasets supporting the conclusions of this article are included within the article and the supplementary information files, or are available on reasonable request. LIMITATIONS, REASONS FOR CAUTION Data are derived from fresh tissue samples and expression levels are an average of expression from different cell types within the endometrium. Subtle cell-specifc expression changes may not be detected and differences in cell composition between samples and across the menstrual cycle will contribute to sample variability. Power to detect tissue specific eQTLs and differences between women with and without endometriosis was limited by the sample size in this study. The statistical approaches used in this study identify the likely gene targets for specific genetic risk factors, but not the functional mechanism by which changes in gene expression may influence disease risk. WIDER IMPLICATIONS OF THE FINDINGS Our results identify novel genetic variants that regulate gene expression in endometrium and the majority of these are shared across tissues. This allows analysis with large publicly available datasets to identify targets for female reproductive traits and diseases. Much larger studies will be required to identify genetic regulation of gene expression that will be specific to endometrium. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Health and Medical Research Council (NHMRC) under project grants GNT1026033, GNT1049472, GNT1046880, GNT1050208, GNT1105321, GNT1083405 and GNT1107258. G.W.M is supported by a NHMRC Fellowship (GNT1078399). J.Y is supported by an ARC Fellowship (FT180100186). There are no competing interests.
Published: 2020
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33. Additional file 2 of Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Author: Restuadi, Restuadi, Steyn, Frederik J., Kabashi, Edor, Ngo, Shyuan T., Cheng, Fei-Fei, Nabais, Marta F., Thompson, Mike J., Qi, Ting, Wu, Yang, Henders, Anjali K., Wallace, Leanne, Bye, Chris R., Turner, Bradley J., Ziser, Laura, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Schultz, David, Kiernan, Matthew C., van Rheenen, Wouter, van den Berg, Leonard H., Veldink, Jan H., Ophoff, Roel, Gusev, Alexander, Zaitlen, Noah, McRae, Allan F., Henderson, Robert D., Wray, Naomi R., Giacomotto, Jean, and Garton, Fleur C.
Abstract: Additional file 2: Supplementary Methods and Figures. Fig. S1. Functional Annotation and Mapping (FUMA) histogram summary. Fig. S2. Functional Annotation and Mapping (FUMA) gene expression heat map. Fig. S3. S-LDSC annotation enrichment in ALS GWAS. Fig. S4. S-LDSC finds CNS and musculoskeletal cell-type categories are enriched in ALS GWAS. Fig. S5. Summary statistics-based Mendelian Randomisation (SMR) analysis identifies GPX3 and TNIP1. Fig. S6. TWAS-CONTENT full model GPX3 and TNIP1 gene expression variance. Fig. S7. Gene correlation across tissues. Fig. S8. Microarray expression data of TNIP1 and GPX3 demonstrate no difference in expression between cases and controls or genotype. Fig. S9. Preliminary Discovery cohort data demonstrated association with GPX3 and ALS. Fig. S10. Replication GPX3 cohort. Fig. S11. Preliminary longitudinal data assessment of ALSFRS-R and GPX3 levels. Fig. S12. TNIP1 and GPX3 methylation in ALS and control blood. Fig. S13. Knockdown of GPX3 and TNIP1 in human motor neurons. Fig. S14. Motor and developmental effect of GPX3 overexpression in zebrafish. Fig. S15. Effect-size sensitivity analysis. Fig. S16. GPX and GPX3 expression pattern across tissues. Fig. S17. Gpx3 amplicon for danio rerio. Fig. S18. pME-dre_gpx3_Codon_optimised plasmid.
Published: 2022
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34. A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts

Author: Guiyan Ni, Jian Zeng, Joana A. Revez, Ying Wang, Zhili Zheng, Tian Ge, Restuadi Restuadi, Jacqueline Kiewa, Dale R. Nyholt, Jonathan R.I. Coleman, Jordan W. Smoller, Jian Yang, Peter M. Visscher, Naomi R. Wray, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Psychosis Endophenotypes International Consortium, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Kari Stefansson, Wellcome Trust Case-Control Consortium, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O’Donovan, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Héléna A. Gaspar, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Paul F. O’Reilly, Hogni Oskarsson, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, John P. Rice, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Fabian Streit, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Yunpeng Wang, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Katharina Domschke, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Preben Bo Mortensen, Merete Nordentoft, Sara A. Paciga, Nancy L. Pedersen, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Ni, Guiyan, Zeng, Jian, Revez, Joana A., Wang, Ying, Zhili, Zheng, Ge, Tian, Restuadi, Restuadi, Kiewa, Jacqueline, Nyholt, Dale R, Coleman, Jonathan RI, Smoller, Jordan W, Lee, S Hong, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Econometrics, Psychiatry, Department of Technology and Operations Management, Child and Adolescent Psychiatry / Psychology, Epidemiology, Erasmus MC other, Urology, Internal Medicine, Medical Informatics, Immunology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Multifactorial Inheritance, medicine.medical_specialty, LDpred2, BF, Genomics, Disease, Major depressive disorder, risk prediction, 03 medical and health sciences, 0302 clinical medicine, MegaPRS, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genetic risk, Psychiatry, Biological Psychiatry, Genetic association, Depressive Disorder, Major, business.industry, Mental Disorders, medicine.disease, Genetic architecture, Polygenic scores, Risk prediction, polygenic scores, PRS-CS, psychiatric disorders, 030104 developmental biology, SBayesR, Schizophrenia, Cohort, Lassosum, RC0321, business, Psychiatric disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BACKGROUND: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.METHODS: The Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared.RESULTS: Compared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively.CONCLUSIONS: Although the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.
Published: 2021
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35. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: Rheenen, Wouter van, Spek, Rick A. A. van der, Bakker, Mark K., Vugt, Joke J. F. A. van, Hop, Paul J., Zwamborn, Ramona A. J., Klein, Niek de, Westra, Harm Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Needham, Merrilee, Ceroni, Mauro, Simoncini, Costanza, Gagliardi, Stella, Corrado, Lucia, Garton, Fleur C., Mazzini, Letizia, Westeneng, Henk Jan, Ross, Jay P., Valluzzi, Francesco, Aguggia, Marco, Raggi, Flavia, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Ngo, Shyuan T., Corcia, Philippe, Olsen, Catherine M., Hofman, Albert, Van Eijk, Kristel R., Pasterkamp, R. Jeroen, Tittmann, Lukas, Iacoangeli, Alfredo, Mitne Neto, Miguel, Sproviero, Daisy, Cauchi, Ruben J., Ophoff, Roel A., Wiedau Pazos, Martina, Lomen-Hoerth, Catherine, Deerlin, Vivianna M. van, Nicholson, Garth A., Brylev, Lev, Whiteman, David C., Grosskreutz, Julian, Fan, Dongsheng, Couratier, Philippe, Roediger, Annekathrin, Gaur, Nayana, D’alfonso, Sandra, Uitterlinden, André G., Pamphlett, Roger, Fominykh, Vera, Byrne, Ross P., Lieb, Wolfgang, Iazzolino, Barbara, Dekker, Annelot M., Slap Consortium, Demeshonok, Vera, Millecamps, Stéphanie, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Franke, Andre, Mcrae, Allan F., Rowe, Dominic B., Peotta, Laura, Cooper-Knock, Johnathan, Glavač, Damjan, Doherty, Mark, Rietschel, Marcella, Stević, Zorica, Drory, Vivian, Meininger, Vincent, Zarrelli, Michele, Povedano, Monica, Gaunt, Tom R., Steyn, Frederik J., Williams, Kelly L., Smith, Bradley N., Cugnasco, Paolo, Papurello, Diego Maria, Nozzoli, Cecilia, Sorarù, Gianni, Mather, Karen A., Ripke, Stephan, Nöthen, Markus M., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, Carvalho, Mamede de, Gromicho, Marta, Pinto, Susana, Marco, Giovanni de, Al Khleifat, Ahmad, Eberle, Michael A., Braun, Alice, Gusmaroli, Graziano, Siciliano, Gabriele, Petri, Susanne, Breen, Gerome, Weber, Markus, Rouleau, Guy A., Rojas García, Ricardo, Silani, Vincenzo, Amouyel, Philippe, Ghiglione, Paolo, Davey Smith, George, Curtis, Charles J., Shatunov, Aleksey, Mill, Jonathan, Mclaughlin, Russell L., Filosto, Massimiliano, Comi, Cristoforo, Gerfo, Annalisa lo, Ferlini, Alessandra, Riva, Nilo, Mora Pardina, Jesus S., Chiveri, Luca, Hardiman, Orla, Torrieri, Maria Claudia, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Padovani, Alessandro, Chandran, Siddharthan, Al Chalabi, Ammar, Assialioui, Abdelilah, Labate, Carmelo, Damme, Philip van, Ticozzi, Nicola, Palumbo, Francesca, Inghilleri, Maurizio, Chiò, Adriano, Pal, Suvankar, Lunetta, Christian, Jörk, Alexander, Cichon, Sven, Kraft, Julia, Morrison, Karen E., Ruiz, Luigi, Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Dion, Patrick A., Calvo, Andrea, Kooyman, Maarten, Başak, Nazli, Gerardi, Francesca, Simone, Isabella L., Kooi, Anneke J. van der, Ratti, Antonia, Ferrandi, Delfina, Fogh, Isabella, Ludolph, Albert C., Moglia, Cristina, Brunetti, Maura, Diamanti, Luca, Barthel, Tabea, Blair, Ian P., Es, Michael A. van, Gallone, Salvatore, Canosa, Antonio, Guerra, Vito, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Ferrarese, Carlo, Nefussy, Beatrice, Theele, Erik, Rinaldi, Fabrizio, Weishaupt, Jochen H., Kiernan, Matthew C., Barberis, Marco, Osmanovic, Alma, Baloh, Robert H., Nordin, Angelica, Lerner, Yossef, Vito, Nicoletta di, Zabari, Michal, Zoccolella, Stefano, Heverin, Mark, Gotkine, Marc, Guaita, Maria Cristina, Brenner, David, Freischmidt, Axel, Sbaiz, Luca, Benyamin, Beben, Glass, Jonathan D., Landers, John E., Tazelaar, Gijs H. P., Rota, Eugenia, Bensimon, Gilbert, Ilse, Benjamin, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Gentile, Salvatore, Moisse, Matthieu, Topp, Simon, Henderson, Robert D., Rademakers, Rosa, Perrone, Patrizia, Stubendorff, Beatrice, Brown, Robert H., Restuadi, Restuadi, Tremolizzo, Lucio, Mundi, Ciro, Berg, Leonard H. van den, Passarella, Bruno, Delodovici, Maria Luisa, Furlong, Sarah, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Meineri, Piero, Mauro, Alessandro, Hannon, Eilis, Casale, Federico, Leone, Maurizio, Shaw, Christopher E., Fuda, Giuseppe, Salamone, Paolina, Mathers, Susan, Baird, Denis, Launaro, Nicola, Marchi, Fabiola de, Veldink, Jan H., Gellera, Cinzia, Salachas, François, Witte, Otto W., Andersen, Peter M., Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Slalom Consortium, Tamma, Filippo, Dotta, Michele, Lauria, Giuseppe, Steinbach, Robert, Imperiale, Daniele, Geda, Claudio, Dolzhenko, Egor, Cavallo, Roberto, Pignatta, Pietro, Groen, Ewout J. N., Cotelli, Maria Sofia, Mattei, Marco de, Calabrese, Gianluigi, Sapio, Alessia di, Giardini, Guido, Hübner, Christian A., Corti, Stefania, Bell, Shaughn, Comi, Giancarlo, Mccombe, Pamela A., Tiloca, Cinzia, Parals Consortium, Gawor, Klara, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Graff, Caroline, Comi, Giacomo P., Cereda, Cristina, Bo, Roberto del, Boero, Giovanni, Slagen Consortium, Vourc’h, Patrick, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), van Rheenen, Wouter, van der Spek, Rick AA, Bakker, Mark K, van Vugt, Joke JFA, Benyamin, Beben, Veldink, Jan H, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, SLAP Consortium, van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, Ferrarese, C, Neurology, ANS - Neuroinfection & -inflammation, APH - Methodology, APH - Quality of Care, EURO-NMD, Internal Medicine, Epidemiology, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W., Van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H.J., Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H.J., Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D'Alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc'h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Kraft, J.,Whiteman, David C., Olsen, Catherine M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nothen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Neto, M.M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jork, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hubner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavac, M., Glavac, D., Stevic, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A, Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N, van Es, M.A., Pasterkamp, R.J., Fan, D.S., Garton, F.C., McRae, A.F., Smith, G.D., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E.L., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
Subjects: Male, Genetics and heredity, amyotrophic lateral sclerosis, Neurologi, Glutamine, Medizin, Genome-wide association study, Disease, SUSCEPTIBILITY, Genome-wide association studies, DISEASE, Genètica mèdica, 0302 clinical medicine, neurodegenerative disease, genome-wide association study, ALS, gene, autophagy, Risk Factors, amyotrophic lateral sclerosi, RNA-Seq, Amyotrophic lateral sclerosis, disease-modifying therapies, blood [Cholesterol], Genetics, Genetics & Heredity, Neurons, 0303 health sciences, Medical genetics, Neurodegenerative diseases, Genome-wide association, Mendelian randomization, Frontotemporal dementia, Hexanucleotide repeat, Mutant SOD1, Metaanalysis, ALS, Susceptibility, Identification, Brain, Amyotrophic Lateral Sclerosis, Cholesterol, Disease Progression, Female, Humans, Mendelian Randomization Analysis, Microsatellite Repeats, Neurodegenerative Diseases, Quantitative Trait Loci, Genome-Wide Association Study, Mutation, MUTANT SOD1, genetics [Amyotrophic Lateral Sclerosis], medicine.anatomical_structure, Neurology, risk factor, metabolism [Neurons], MENDELIAN RANDOMIZATION, nerve cell, Life Sciences & Biomedicine, quantitative trait locu, Biology, 03 medical and health sciences, Amyotrophic lateral sclerosis -- Diagnosis, blood, ddc:570, medicine, degenerative disease, Motor neuron disease, human, Genomes, GENOME-WIDE ASSOCIATION, gene, Gene, metabolism [Glutamine], METAANALYSIS, 030304 developmental biology, Mendelian randomization analysi, Science & Technology, HEXANUCLEOTIDE REPEAT, meta analysi, IDENTIFICATION, metabolism [Amyotrophic Lateral Sclerosis], FRONTOTEMPORAL DEMENTIA, medicine.disease, metabolism [Brain], genetics [Neurodegenerative Diseases], Expression quantitative trait loci, disease exacerbation, Neuron, gemone, genetic, Vesicle-mediated transport, metabolism, Nervous system -- Degeneration, Esclerosi lateral amiotròfica, 030217 neurology & neurosurgery
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons., Dutch Research Council (NWO); VENI Scheme Grant; VIDI Grant; Prinses Beatrix Spierfonds; Neuromuscular Fellowship Grant; Medical Research Council (MRC); Clinical Infrastructure Award; Epidemiology Unit; Integrative Epidemiology Unit; Canadian Institutes of Health Research; IWT; National Institute on Aging; National Health and Medical Research Council (NHMRC); Enabling Grant; NHMRC/Australian Research Council Strategic Award; NHMRC; NHMRC Centre of Research Excellence Grant; National Health and Medical Research Council of Australia (NHMRC) Research Fellowship; United Kingdom, Medical Research Council; Economic and Social Research Council; European Union (EU); Horizon 2020; European Community's Health Seventh Framework Programme; EuroMOTOR; European Research Council (ERC); Research and Innovation Programme; EScORIAL; ALS Foundation Netherlands; Alzheimer’s Society PhD Studentship; ARSla Funding; Biogen; University of Bristol; Motor Neurone Disease Association (MNDA); NIHR Maudsley Biomedical Research Centre; Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO; BRAINSCAPES); Gravitation Program; ALS Liga België; National Lottery of Belgium; KU Leuven Opening the Future Fund; KU Leuven Funds, “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders; ALS Liga België; “Live now” Charity Foundation; Moscow ALS palliative Care Service; Canadian Institutes of Health; Research Australia; Ice Bucket Challenge Grant; NIH Intramural Research Programs; FightMND Mid-Career Fellowship; NIHR Senior Investigator; Sheffield NIHR Biomedical Research Centre; Motor Neurone Disease Association; National Institute for Health Research (NIHR) Biomedical Research Centre; Maudsley NHS Foundation Trust; King’s College London; NIHR Senior Investigator Award; Netherlands Organization for Health Research and Development; Vici Scheme; Netherlands Organization for Health Research and Development STRENGTH Project; PPP Allowance
Published: 2021
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36. A Comparison of Ten Polygenic Score Methods for Psychiatric Disorders Applied Across Multiple Cohorts

Author: Ni, Guiyan, primary, Zeng, Jian, additional, Revez, Joana A., additional, Wang, Ying, additional, Zheng, Zhili, additional, Ge, Tian, additional, Restuadi, Restuadi, additional, Kiewa, Jacqueline, additional, Nyholt, Dale R., additional, Coleman, Jonathan R.I., additional, Smoller, Jordan W., additional, Yang, Jian, additional, Visscher, Peter M., additional, Wray, Naomi R., additional, Ripke, Stephan, additional, Neale, Benjamin M., additional, Corvin, Aiden, additional, Walters, James T.R., additional, Farh, Kai-How, additional, Holmans, Peter A., additional, Lee, Phil, additional, Bulik-Sullivan, Brendan, additional, Collier, David A., additional, Huang, Hailiang, additional, Pers, Tune H., additional, Agartz, Ingrid, additional, Agerbo, Esben, additional, Albus, Margot, additional, Alexander, Madeline, additional, Amin, Farooq, additional, Bacanu, Silviu A., additional, Begemann, Martin, additional, Belliveau, Richard A., additional, Bene, Judit, additional, Bergen, Sarah E., additional, Bevilacqua, Elizabeth, additional, Bigdeli, Tim B., additional, Black, Donald W., additional, Bruggeman, Richard, additional, Buccola, Nancy G., additional, Buckner, Randy L., additional, Byerley, William, additional, Cahn, Wiepke, additional, Cai, Guiqing, additional, Campion, Dominique, additional, Cantor, Rita M., additional, Carr, Vaughan J., additional, Carrera, Noa, additional, Catts, Stanley V., additional, Chambert, Kimberley D., additional, Chan, Raymond C.K., additional, Chen, Ronald Y.L., additional, Chen, Eric Y.H., additional, Cheng, Wei, additional, Cheung, Eric F.C., additional, Chong, Siow Ann, additional, Cloninger, C. Robert, additional, Cohen, David, additional, Cohen, Nadine, additional, Cormican, Paul, additional, Craddock, Nick, additional, Crowley, James J., additional, Davidson, Michael, additional, Davis, Kenneth L., additional, Degenhardt, Franziska, additional, Del Favero, Jurgen, additional, Demontis, Ditte, additional, Dikeos, Dimitris, additional, Dinan, Timothy, additional, Djurovic, Srdjan, additional, Donohoe, Gary, additional, Drapeau, Elodie, additional, Duan, Jubao, additional, Dudbridge, Frank, additional, Durmishi, Naser, additional, Eichhammer, Peter, additional, Eriksson, Johan, additional, Escott-Price, Valentina, additional, Essioux, Laurent, additional, Fanous, Ayman H., additional, Farrell, Martilias S., additional, Frank, Josef, additional, Franke, Lude, additional, Freedman, Robert, additional, Freimer, Nelson B., additional, Friedl, Marion, additional, Friedman, Joseph I., additional, Fromer, Menachem, additional, Genovese, Giulio, additional, Georgieva, Lyudmila, additional, Giegling, Ina, additional, Giusti-Rodríguez, Paola, additional, Godard, Stephanie, additional, Goldstein, Jacqueline I., additional, Golimbet, Vera, additional, Gopal, Srihari, additional, Gratten, Jacob, additional, de Haan, Lieuwe, additional, Hammer, Christian, additional, Hamshere, Marian L., additional, Hansen, Mark, additional, Hansen, Thomas, additional, Haroutunian, Vahram, additional, Hartmann, Annette M., additional, Henskens, Frans A., additional, Herms, Stefan, additional, Hirschhorn, Joel N., additional, Hoffmann, Per, additional, Hofman, Andrea, additional, Hollegaard, Mads V., additional, Hougaard, David M., additional, Ikeda, Masashi, additional, Joa, Inge, additional, Julià, Antonio, additional, Kahn, René S., additional, Kalaydjieva, Luba, additional, Karachanak-Yankova, Sena, additional, Karjalainen, Juha, additional, Kavanagh, David, additional, Keller, Matthew C., additional, Kennedy, James L., additional, Khrunin, Andrey, additional, Kim, Yunjung, additional, Klovins, Janis, additional, Knowles, James A., additional, Konte, Bettina, additional, Kucinskas, Vaidutis, additional, Kucinskiene, Zita Ausrele, additional, Kuzelova-Ptackova, Hana, additional, Kähler, Anna K., additional, Laurent, Claudine, additional, Lee, Jimmy, additional, Lee, S. Hong, additional, Legge, Sophie E., additional, Lerer, Bernard, additional, Li, Miaoxin, additional, Li, Tao, additional, Liang, Kung-Yee, additional, Lieberman, Jeffrey, additional, Limborska, Svetlana, additional, Loughland, Carmel M., additional, Lubinski, Jan, additional, Lönnqvist, Jouko, additional, Macek, Milan, additional, Magnusson, Patrik K.E., additional, Maher, Brion S., additional, Maier, Wolfgang, additional, Mallet, Jacques, additional, Marsal, Sara, additional, Mattheisen, Manuel, additional, Mattingsdal, Morten, additional, McCarley, Robert W., additional, McDonald, Colm, additional, McIntosh, Andrew M., additional, Meier, Sandra, additional, Meijer, Carin J., additional, Melegh, Bela, additional, Melle, Ingrid, additional, Mesholam-Gately, Raquelle I., additional, Metspalu, Andres, additional, Michie, Patricia T., additional, Milani, Lili, additional, Milanova, Vihra, additional, Mokrab, Younes, additional, Morris, Derek W., additional, Mors, Ole, additional, Murphy, Kieran C., additional, Murray, Robin M., additional, Myin-Germeys, Inez, additional, Müller-Myhsok, Bertram, additional, Nelis, Mari, additional, Nenadic, Igor, additional, Nertney, Deborah A., additional, Nestadt, Gerald, additional, Nicodemus, Kristin K., additional, Nikitina-Zake, Liene, additional, Nisenbaum, Laura, additional, Nordin, Annelie, additional, O’Callaghan, Eadbhard, additional, O’Dushlaine, Colm, additional, O’Neill, F. Anthony, additional, Oh, Sang-Yun, additional, Olincy, Ann, additional, Olsen, Line, additional, Van Os, Jim, additional, International Consortium, Psychosis Endophenotypes, additional, Pantelis, Christos, additional, Papadimitriou, George N., additional, Papiol, Sergi, additional, Parkhomenko, Elena, additional, Pato, Michele T., additional, Paunio, Tiina, additional, Pejovic-Milovancevic, Milica, additional, Perkins, Diana O., additional, Pietiläinen, Olli, additional, Pimm, Jonathan, additional, Pocklington, Andrew J., additional, Powell, John, additional, Price, Alkes, additional, Pulver, Ann E., additional, Purcell, Shaun M., additional, Quested, Digby, additional, Rasmussen, Henrik B., additional, Reichenberg, Abraham, additional, Reimers, Mark A., additional, Richards, Alexander L., additional, Roffman, Joshua L., additional, Roussos, Panos, additional, Ruderfer, Douglas M., additional, Salomaa, Veikko, additional, Sanders, Alan R., additional, Schall, Ulrich, additional, Schubert, Christian R., additional, Schulze, Thomas G., additional, Schwab, Sibylle G., additional, Scolnick, Edward M., additional, Scott, Rodney J., additional, Seidman, Larry J., additional, Shi, Jianxin, additional, Sigurdsson, Engilbert, additional, Silagadze, Teimuraz, additional, Silverman, Jeremy M., additional, Sim, Kang, additional, Slominsky, Petr, additional, So, Hon-Cheong, additional, Spencer, Chris C.A., additional, Stahl, Eli A., additional, Stefansson, Hreinn, additional, Steinberg, Stacy, additional, Stogmann, Elisabeth, additional, Straub, Richard E., additional, Strengman, Eric, additional, Strohmaier, Jana, additional, Stroup, T. Scott, additional, Subramaniam, Mythily, additional, Suvisaari, Jaana, additional, Svrakic, Dragan M., additional, Szatkiewicz, Jin P., additional, Söderman, Erik, additional, Thirumalai, Srinivas, additional, Toncheva, Draga, additional, Tosato, Sarah, additional, Veijola, Juha, additional, Waddington, John, additional, Walsh, Dermot, additional, Wang, Dai, additional, Wang, Qiang, additional, Webb, Bradley T., additional, Weiser, Mark, additional, Wildenauer, Dieter B., additional, Williams, Nigel M., additional, Williams, Stephanie, additional, Witt, Stephanie H., additional, Wolen, Aaron R., additional, Wong, Emily H.M., additional, Wormley, Brandon K., additional, Xi, Hualin Simon, additional, Zai, Clement C., additional, Zheng, Xuebin, additional, Zimprich, Fritz, additional, Stefansson, Kari, additional, Case-Control Consortium, Wellcome Trust, additional, Adolfsson, Rolf, additional, Andreassen, Ole A., additional, Blackwood, Douglas H.R., additional, Bramon, Elvira, 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Posthuma, Danielle, additional, Rietschel, Marcella, additional, Riley, Brien P., additional, Rujescu, Dan, additional, Sham, Pak C., additional, Sklar, Pamela, additional, St Clair, David, additional, Weinberger, Daniel R., additional, Wendland, Jens R., additional, Werge, Thomas, additional, Daly, Mark J., additional, Sullivan, Patrick F., additional, O’Donovan, Michael C., additional, Trzaskowski, Maciej, additional, Byrne, Enda M., additional, Abdellaoui, Abdel, additional, Adams, Mark J., additional, Air, Tracy M., additional, Andlauer, Till F.M., additional, Bacanu, Silviu-Alin, additional, Bækvad-Hansen, Marie, additional, Beekman, Aartjan T.F., additional, Binder, Elisabeth B., additional, Bryois, Julien, additional, Buttenschøn, Henriette N., additional, Bybjerg-Grauholm, Jonas, additional, Cai, Na, additional, Castelao, Enrique, additional, Christensen, Jane Hvarregaard, additional, Clarke, Toni-Kim, additional, Colodro-Conde, Lucía, additional, Couvy-Duchesne, Baptiste, additional, Crawford, Gregory E., additional, Davies, Gail, additional, Deary, Ian J., additional, Derks, Eske M., additional, Direk, Nese, additional, Dolan, Conor V., additional, Dunn, Erin C., additional, Eley, Thalia C., additional, Hassan Kiadeh, Farnush Farhadi, additional, Finucane, Hilary K., additional, Foo, Jerome C., additional, Forstner, Andreas J., additional, Gaspar, Héléna A., additional, Goes, Fernando S., additional, Gordon, Scott D., additional, Grove, Jakob, additional, Hall, Lynsey S., additional, Hansen, Christine Søholm, additional, Hansen, Thomas F., additional, Hickie, Ian B., additional, Homuth, Georg, additional, Horn, Carsten, additional, Hottenga, Jouke-Jan, additional, Howard, David M., additional, Ising, Marcus, additional, Jansen, Rick, additional, Jones, Ian, additional, Jones, Lisa A., additional, Jorgenson, Eric, additional, Kohane, Isaac S., additional, Kraft, Julia, additional, Kretzschmar, Warren W., additional, Kutalik, Zoltán, additional, Li, Yihan, additional, Lind, Penelope A., additional, MacIntyre, Donald J., additional, MacKinnon, Dean F., additional, Maier, Robert M., additional, Marchini, Jonathan, additional, Mbarek, Hamdi, additional, McGrath, Patrick, additional, McGuffin, Peter, additional, Medland, Sarah E., additional, Mehta, Divya, additional, Middeldorp, Christel M., additional, Mihailov, Evelin, additional, Milaneschi, Yuri, additional, Mondimore, Francis M., additional, Montgomery, Grant W., additional, Mostafavi, Sara, additional, Mullins, Niamh, additional, Nauck, Matthias, additional, Ng, Bernard, additional, Nivard, Michel G., additional, O’Reilly, Paul F., additional, Oskarsson, Hogni, additional, Painter, Jodie N., additional, Pedersen, Carsten Bøcker, additional, Pedersen, Marianne Giørtz, additional, Peterson, Roseann E., additional, Peyrot, Wouter J., additional, Pistis, Giorgio, additional, Quiroz, Jorge A., additional, Qvist, Per, additional, Rice, John P., additional, Rivera, Margarita, additional, Mirza, Saira Saeed, additional, Schoevers, Robert, additional, Schulte, Eva C., additional, Shen, Ling, additional, Shyn, Stanley I., additional, Sinnamon, Grant C.B., additional, Smit, Johannes H., additional, Smith, Daniel J., additional, Streit, Fabian, additional, Tansey, Katherine E., additional, Teismann, Henning, additional, Teumer, Alexander, additional, Thompson, Wesley, additional, Thomson, Pippa A., additional, Thorgeirsson, Thorgeir E., additional, Traylor, Matthew, additional, Treutlein, Jens, additional, Trubetskoy, Vassily, additional, Uitterlinden, André G., additional, Umbricht, Daniel, additional, Van der Auwera, Sandra, additional, van Hemert, Albert M., additional, Viktorin, Alexander, additional, Wang, Yunpeng, additional, Weinsheimer, Shantel Marie, additional, Wellmann, Jürgen, additional, Willemsen, Gonneke, additional, Wu, Yang, additional, Xi, Hualin S., additional, Zhang, Futao, additional, Arolt, Volker, additional, Baune, Bernhard T., additional, Berger, Klaus, additional, Boomsma, Dorret I., additional, Dannlowski, Udo, additional, de Geus, E.J.C., additional, DePaulo, J. Raymond, additional, Domschke, Katharina, additional, Grabe, Hans J., additional, Hamilton, Steven P., additional, Hayward, Caroline, additional, Heath, Andrew C., additional, Kloiber, Stefan, additional, Lewis, Glyn, additional, Lucae, Susanne, additional, Madden, Pamela A.F., additional, Magnusson, Patrik K., additional, Martin, Nicholas G., additional, Mortensen, Preben Bo, additional, Nordentoft, Merete, additional, Paciga, Sara A., additional, and Pedersen, Nancy L., additional
Published: 2021
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37. Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia

Author: Elizabeth L. Prado, Safarina G. Malik, Restuadi Restuadi, Diana Elizabeth Waturangi, Anuraj H. Shankar, and Lidwina Priliani
Subjects: Adult, 0301 basic medicine, DNA Copy Number Variations, Medicine (miscellaneous), Physiology, Mismatch negativity, DNA, Mitochondrial, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Pregnancy, law, Humans, Medicine, Micronutrients, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Fetus, Nutrition and Dietetics, business.industry, Venous blood, Micronutrient, medicine.disease, Oxidative Stress, Low birth weight, 030104 developmental biology, Real-time polymerase chain reaction, Indonesia, Dietary Supplements, Female, medicine.symptom, business
Abstract: Author(s): Priliani, Lidwina; Prado, Elizabeth L; Restuadi, Restuadi; Waturangi, Diana E; Shankar, Anuraj H; Malik, Safarina G | Abstract: BackgroundThe Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood.ObjectiveThe aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN).MethodsWe used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models.ResultsIn both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P l 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (β = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (β = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (β = -7.39, P = 0.017).ConclusionMaternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.
Published: 2019
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38. Gut microbiota in ALS: possible role in pathogenesis?

Author: Allan F. McRae, Trent M. Woodruff, Pamela A. McCombe, Robert D. Henderson, Naomi R. Wray, John D. Lee, Frederik J. Steyn, Aven Lee, Shyuan T. Ngo, and Restuadi Restuadi
Subjects: Context (language use), Gut flora, Bioinformatics, digestive system, Pathogenesis, 03 medical and health sciences, Human health, 0302 clinical medicine, medicine, Animals, Humans, Pharmacology (medical), Microbiome, Amyotrophic lateral sclerosis, biology, General Neuroscience, Amyotrophic Lateral Sclerosis, digestive, oral, and skin physiology, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, 030227 psychiatry, Dysbiosis, Neurology (clinical), Gut dysbiosis, 030217 neurology & neurosurgery
Abstract: Introduction: The gut microbiota has important roles in maintaining human health. The microbiota and its metabolic byproducts could play a role in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Areas covered: The authors evaluate the methods of assessing the gut microbiota, and also review how the gut microbiota affects the various physiological functions of the gut. The authors then consider how gut dysbiosis could theoretically affect the pathogenesis of ALS. They present the current evidence regarding the composition of the gut microbiota in ALS and in rodent models of ALS. Finally, the authors review therapies that could improve gut dysbiosis in the context of ALS. Expert opinion: Currently reported studies suggest some instances of gut dysbiosis in ALS patients and mouse models; however, these studies are limited, and more information with well-controlled larger datasets is required to make a definitive judgment about the role of the gut microbiota in ALS pathogenesis. Overall this is an emerging field that is worthy of further investigation. The authors advocate for larger studies using modern metagenomic techniques to address the current knowledge gaps.
Published: 2019
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39. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A A, Shireby, Gemma, Whiteman, David C, Olsen, Catherine M, Uitterlinden, Andre G, Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Consortium, SLALOM, Consortium, PARALS, Hannon, Eilis, Consortium, SLAGEN, Consortium, SLAP, Traynor, Bryan J, Singleton, Andrew B, Mitne Neto, Miguel, Cauchi, Ruben J, Ophoff, Roel A, Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M, Moisse, Matthieu, Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W, Steinbach, Robert, Baird, Denis, Hübner, Christian A, Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Restuadi, Restuadi, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P, Kiernan, Matthew C, Benyamin, Beben, Henderson, Robert D, Furlong, Sarah, Mathers, Susan, Dolzhenko, Egor, McCombe, Pamela A, Needham, Merrilee, Ngo, Shyuan T, Nicholson, Garth A, Pamphlett, Roger, Rowe, Dominic B, Steyn, Frederik J, Williams, Kelly L, Mather, Karen A, Sachdev, Perminder S, Dekker, Annelot M, Henders, Anjali K, Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A, Silani, Vincenzo, Curtis, Charles J, Breen, Gerome, Gawor, Klara, Glass, Jonathan D, Brown, Robert H, Landers, John E, Shaw, Christopher E, Andersen, Peter M, Groen, Ewout J N, van Es, Michael A, Pasterkamp, R Jeroen, Fan, Dongsheng, Garton, Fleur C, Westeneng, Henk-Jan, McRae, Allan F, Davey Smith, George, Gaunt, Tom R, Eberle, Michael A, Mill, Jonathan, McLaughlin, Russell L, Hardiman, Orla, Kenna, Kevin P, Wray, Naomi R, Tsai, Ellen, Tazelaar, Gijs H P, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H, Veldink, Jan H, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Bakker, Mark K, van Eijk, Kristel R, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Kooyman, Maarten, Bono, Giorgio, Canosa, Antonio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Byrne, Ross P, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, Doherty, Mark, De Marchi, Fabiola, Corrado, Lucia, D'Alfonso, Sandra, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, Heverin, Mark, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Al Khleifat, Ahmad, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Iacoangeli, Alfredo, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P, Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Shatunov, Aleksey, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L, Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Ticozzi, Nicola, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Cooper-Knock, Johnathan, van Vugt, Joke J F A, Smith, Bradley N, Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Sendtner, Michael, Meyer, Thomas, Hop, Paul J, Başak, Nazli, van der Kooi, Anneke J, Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, Zwamborn, Ramona A J, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Grassano, Maurizio, de Klein, Niek, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H, Westra, Harm-Jan, Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S, Assialioui, Abdelilah, Rojas-García, Ricardo, Bakker, Olivier B, Dion, Patrick A, Ross, Jay P, Ludolph, Albert, Weishaupt, Jochen H, Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Dürr, Alexandra, Payan, Christine A M, Deelen, Patrick, Saker-Delye, Safa, Wood, Nicholas W, Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, and Kraft, Julia
Subjects: ddc:570, Genetics, Medizin
Abstract: In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.
Published: 2021
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40. Autism-related dietary preferences mediate autism-gut microbiome associations

Author: Yap, Chloe X, Henders, Anjali K, Alvares, Gail A, Wood, David L A, Krause, Lutz, Tyson, Gene W, Restuadi, Restuadi, Wallace, Leanne, McLaren, Tiana, Hansell, Narelle K, Cleary, Dominique, Grove, Rachel, Hafekost, Claire, Harun, Alexis, Holdsworth, Helen, Jellett, Rachel, Khan, Feroza, Lawson, Lauren P, Leslie, Jodie, Frenk, Mira Levis, Masi, Anne, Mathew, Nisha E, Muniandy, Melanie, Nothard, Michaela, Miller, Jessica L, Nunn, Lorelle, Holtmann, Gerald, Strike, Lachlan T, de Zubicaray, Greig I, Thompson, Paul M, McMahon, Katie L, Wright, Margaret J, Visscher, Peter M, Dawson, Paul A, Dissanayake, Cheryl, Eapen, Valsamma, Heussler, Helen S, McRae, Allan F, Whitehouse, Andrew J O, Wray, Naomi R, Gratten, Jacob, Yap, Chloe X, Henders, Anjali K, Alvares, Gail A, Wood, David L A, Krause, Lutz, Tyson, Gene W, Restuadi, Restuadi, Wallace, Leanne, McLaren, Tiana, Hansell, Narelle K, Cleary, Dominique, Grove, Rachel, Hafekost, Claire, Harun, Alexis, Holdsworth, Helen, Jellett, Rachel, Khan, Feroza, Lawson, Lauren P, Leslie, Jodie, Frenk, Mira Levis, Masi, Anne, Mathew, Nisha E, Muniandy, Melanie, Nothard, Michaela, Miller, Jessica L, Nunn, Lorelle, Holtmann, Gerald, Strike, Lachlan T, de Zubicaray, Greig I, Thompson, Paul M, McMahon, Katie L, Wright, Margaret J, Visscher, Peter M, Dawson, Paul A, Dissanayake, Cheryl, Eapen, Valsamma, Heussler, Helen S, McRae, Allan F, Whitehouse, Andrew J O, Wray, Naomi R, and Gratten, Jacob
Abstract: There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
Published: 2021

41. A comparison of ten polygenic score methods for psychiatric disorders applied across multiple cohorts

Author: Ni, Guiyan, Zeng, Jian, Revez, Joana A., Wang, Ying, Zheng, Zhili, Ge, Tian, Restuadi, Restuadi, Kiewa, Jacqueline, Nyholt, Dale R., Coleman, Jonathan R.I., Smoller, Jordan W., Yang, Jian, Visscher, Peter M., Wray, Naomi R., Ni, Guiyan, Zeng, Jian, Revez, Joana A., Wang, Ying, Zheng, Zhili, Ge, Tian, Restuadi, Restuadi, Kiewa, Jacqueline, Nyholt, Dale R., Coleman, Jonathan R.I., Smoller, Jordan W., Yang, Jian, Visscher, Peter M., and Wray, Naomi R.
Abstract: Background: Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies. PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors. Methods: The Psychiatric Genomics Consortium Working Groups for schizophrenia and major depressive disorder bring together many independently collected case-control cohorts. We used these resources (31,328 schizophrenia cases, 41,191 controls; 248,750 major depressive disorder cases, 563,184 controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out (target) cohort. Ten PGS methods (the baseline PC+T method and 9 methods that model genetic architecture more formally: SBLUP, LDpred2-Inf, LDpred-funct, LDpred2, Lassosum, PRS-CS, PRS-CS-auto, SBayesR, MegaPRS) were compared. Results: Compared with PC+T, the other 9 methods gave higher prediction statistics, MegaPRS, LDPred2, and SBayesR significantly so, explaining up to 9.2% variance in liability for schizophrenia across 30 target cohorts, an increase of 44%. For major depressive disorder across 26 target cohorts, these statistics were 3.5% and 59%, respectively. Conclusions: Although the methods that more formally model genetic architecture have similar performance, MegaPRS, LDpred2, and SBayesR rank highest in most comparisons and are recommended in applications to psychiatric disorders.
Published: 2021

42. Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

Author: Restuadi, Restuadi, primary, Garton, Fleur C., additional, Benyamin, Beben, additional, Lin, Tian, additional, Williams, Kelly L., additional, Vinkhuyzen, Anna, additional, van Rheenen, Wouter, additional, Zhu, Zhihong, additional, Laing, Nigel G., additional, Mather, Karen A., additional, Sachdev, Perminder S., additional, Ngo, Shyuan T., additional, Steyn, Frederik J., additional, Wallace, Leanne, additional, Henders, Anjali K., additional, Visscher, Peter M., additional, Needham, Merrilee, additional, Mathers, Susan, additional, Nicholson, Garth, additional, Rowe, Dominic B., additional, Henderson, Robert D., additional, McCombe, Pamela A., additional, Pamphlett, Roger, additional, Blair, Ian P., additional, Wray, Naomi R., additional, and McRae, Allan F., additional
Published: 2021
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43. Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics

Author: Robert D. Henderson, Ashley R. Jones, Ian P. Blair, Stephen J. Newhouse, Tian Lin, Roger Pamphlett, Sarah Opie-Martin, Shyuan T. Ngo, Richard Dobson, Perminder S. Sachdev, Dominic B. Rowe, Pamela A. McCombe, Anjali K. Henders, Fleur C. Garton, Jonathan R. I. Coleman, Ammar Al-Chalabi, Aleksey Shatunov, Merilee Needham, Isabella Fogh, Karen A. Mather, Frederik J. Steyn, Alfredo Iacoangeli, Naomi R. Wray, Garth A. Nicholson, Restuadi Restuadi, Ahmad Al Khleifat, Kelly L. Williams, William Sproviero, David Schultz, Susan Mathers, and Petroula Proitsi
Subjects: 0301 basic medicine, Longitudinal study, amyotrophic lateral sclerosis, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Report, Weight Loss, medicine, genomics, Humans, genetics, Genetic Predisposition to Disease, Allele, Amyotrophic lateral sclerosis, Genetics, genome-wide association study, eQTLs, longitudinal study, medicine.disease, fat-free mass, 030104 developmental biology, Cohort, motor neuron disease, cross-ethnic meta-analysis, medicine.symptom, 030217 neurology & neurosurgery, Acyltransferases
Abstract: Summary We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10−9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients’ fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: −2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: −1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients., Graphical Abstract, Highlights • Cross-ethnic meta-analysis finds an association between the ACSL5-ZDHHC6 locus and ALS • The ACSL5-ZDHHC6 association is replicated in an independent Australian cohort • ACSL5-ZDHHC6 lead SNP is in ACSL5 and is an eQTL of ZDHHC6 in brain tissues • ACSL5 SNPs might have an effect on fat-free mass in ALS patients, Using meta-analysis of European and Chinese ALS GWAS data, Iacoangeli et al. find an association between ACSL5-ZDHHC6 and ALS risk, with replication in an Australian cohort. They identify B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 using a gene-based analysis. They also find a suggestive association between ACSL5 SNPs and lower fat-free mass in patients.
Published: 2020

44. Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Author: Anna A. E. Vinkhuyzen, Frederik J. Steyn, Beben Benyamin, Dominic B. Rowe, Tian Lin, Jan H. Veldink, Kelly L. Williams, Ian P. Blair, Merrilee Needham, Roger Pamphlett, Shyuan T. Ngo, Paul J. Hop, Anna Freydenzon, Allan F. McRae, Anjali K. Henders, Marta F. Nabais, Perminder S. Sachdev, Robert D. Henderson, Eilis Hannon, Futao Zhang, Naomi R. Wray, Pamela A. McCombe, Restuadi Restuadi, Matthew A. Brown, Fleur C. Garton, Nigel G. Laing, Peter M. Visscher, Jonathan Mill, Leanne Wallace, Matthew R. Robinson, Jacob Gratten, Garth A. Nicholson, Jian Yang, Susan Mathers, Karen A. Mather, Ramona A. J. Zwamborn, Costanza L. Vallerga, Nabais, Marta F, Lin, Tian, Benyamin, Beben, Williams, Kelly L, and Wray, Naomi R
Subjects: 0301 basic medicine, amyotrophic lateral sclerosis, medicine.medical_specialty, lcsh:QH426-470, lcsh:Medicine, Predictive markers, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, single nucleotide polymorphism, Internal medicine, Genetics, Medicine, Amyotrophic lateral sclerosis, Molecular Biology, Genetics (clinical), DNA methylation, business.industry, lcsh:R, Confounding, Area under the curve, Methylation, cohort analysis, medicine.disease, lcsh:Genetics, 030104 developmental biology, Out of sample, Cohort, business, 030217 neurology & neurosurgery
Abstract: We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.
Published: 2020

45. Progression and survival of patients with motor neuron disease relative to their fecal microbiota

Author: Shyuan T. Ngo, Restuadi Restuadi, McCrae, Allan F., Van Eijk, Ruben P., Garton, Fleur, Henderson, Robert D., Wray, Naomi R., McCombe, Pamela A., and Steyn, Frederik J.
Abstract: Gut microbiota studies have been well-investigated for neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, however, fewer studies have comprehensively examined the gut microbiome in Motor Neuron Disease (MND), with none examining its impact on disease prognosis. Here, we investigate MND prognosis and the fecal microbiota, using 16S rRNA case–control data from 100 individuals with extensive medical histories and metabolic measurements. We contrast the composition and diversity of fecal microbiome signatures from 49 MND and 51 healthy controls by combining current gold-standard 16S microbiome pipelines. Using stringent quality control thresholds, we conducted qualitative assessment approaches including; direct comparison of taxa, PICRUSt2 predicted metagenomics, Shannon and Chao1-index and Firmicutes/Bacteroidetes ratio. We show that the fecal microbiome of patients with MND is not significantly different from that of healthy controls that were matched by age, sex, and BMI, however there are distinct differences in Beta-diversity in some patients with MND. Weight, BMI, and metabolic and clinical features of disease in patients with MND were not related to the composition of their fecal microbiome, however, we observe a greater risk for earlier death in patients with MND with increased richness and diversity of the microbiome, and in those with greater Firmicutes to Bacteroidetes ratio. This was independent of anthropometric, metabolic, or clinical features of disease, and warrants support for further gut microbiota studies in MND. Given the disease heterogeneity in MND, and complexity of the gut microbiota, large studies are necessary to determine the detailed role of the gut microbiota and MND prognosis.
Published: 2020
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46. Functional Characterisation of a GWAS Risk Locus Identifies GPX3 as a Lead Candidate Gene in ALS

Author: Michael J. Thompson, Noah Zaitlen, Edor Kabashi, Naomi R. Wray, Fei-Fei Cheng, Matthew C. Kiernan, Leanne Wallace, Shyuan T. Ngo, David Schultz, Robert D. Henderson, Susan Mathers, Merrilee Needham, Jean Giacomotto, Allan F. McRae, Christopher R. Bye, Leonard H. van den Berg, Bradley J. Turner, Anjali K. Henders, Restuadi Restuadi, Marta F. Nabais, Wouter van Rheenen, Frederik J. Steyn, Laura Ziser, Jan H. Veldink, Alexander Gusev, Ting Qi, Roel A. Ophoff, Pamela A. McCombe, and Fleur C. Garton
Subjects: Candidate gene, Expression quantitative trait loci, medicine, Genome-wide association study, Locus (genetics), Disease, Computational biology, Amyotrophic lateral sclerosis, Biology, medicine.disease, Gene, Genetic association
Abstract: Amyotrophic lateral sclerosis (ALS) is a complex late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies have identified eleven risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Current association analysis data alone cannot determine the most plausible risk gene in this locus. Here, we undertake a comprehensive suite of studies to provide objective evidence to support or reject the relevance of these two genes. We use bioinformatic integration of genetic association data with omics reference data sets, in-vitro and in-vivo approaches to narrow down the likely candidate. TNIP1 and GPX3 are implicated in-silico (rs10463311 is an eQTL for these two genes). In-vivo expression analyses in ALS cases identify that GPX3 expression decreases with increased disability and rate of progression. Validation in-vivo, indicate GPX3 loss-of-function causes motor deficits in zebrafish embryos. Taken together, these results support GPX3 as being the ALS risk gene in this locus which has implications for understanding disease mechanisms and targeted therapeutic approaches.
Published: 2020
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47. Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Author: Neurogenetica, ZL Neuromusculaire Ziekten Medisch, Brain, Nabais, Marta F., Lin, Tian, Benyamin, Beben, Williams, Kelly L., Garton, Fleur C., Vinkhuyzen, Anna A.E., Zhang, Futao, Vallerga, Costanza L., Restuadi, Restuadi, Freydenzon, Anna, Zwamborn, Ramona A.J., Hop, Paul J., Robinson, Matthew R., Gratten, Jacob, Visscher, Peter M., Hannon, Eilis, Mill, Jonathan, Brown, Matthew A., Laing, Nigel G., Mather, Karen A., Sachdev, Perminder S., Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Henders, Anjali K., Needham, Merrilee, Veldink, Jan H., Mathers, Susan, Nicholson, Garth, Rowe, Dominic B., Henderson, Robert D., McCombe, Pamela A., Pamphlett, Roger, Yang, Jian, Blair, Ian P., McRae, Allan F., Wray, Naomi R., Neurogenetica, ZL Neuromusculaire Ziekten Medisch, Brain, Nabais, Marta F., Lin, Tian, Benyamin, Beben, Williams, Kelly L., Garton, Fleur C., Vinkhuyzen, Anna A.E., Zhang, Futao, Vallerga, Costanza L., Restuadi, Restuadi, Freydenzon, Anna, Zwamborn, Ramona A.J., Hop, Paul J., Robinson, Matthew R., Gratten, Jacob, Visscher, Peter M., Hannon, Eilis, Mill, Jonathan, Brown, Matthew A., Laing, Nigel G., Mather, Karen A., Sachdev, Perminder S., Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Henders, Anjali K., Needham, Merrilee, Veldink, Jan H., Mathers, Susan, Nicholson, Garth, Rowe, Dominic B., Henderson, Robert D., McCombe, Pamela A., Pamphlett, Roger, Yang, Jian, Blair, Ian P., McRae, Allan F., and Wray, Naomi R.
Published: 2020

48. Common and rare variant association analyses in Amyotrophic Lateral Sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: Rheenen, Wouter van, primary, Spek, Rick van der, additional, Bakker, Mark, additional, Berg, Leonard van den, additional, Veldink, Jan, additional, Vugt, Joke van, additional, Hop, Paul, additional, Zwamborn, Ramona, additional, de Klein, Niek, additional, Westra, Harm-Jan, additional, Bakker, Olivier, additional, Deelen, Patrick, additional, Shireby, Gemma, additional, Hannon, Eilis, additional, Moisse, Matthieu, additional, Baird, Denis, additional, Restuadi, Restuadi, additional, Dolzhenko, Egor, additional, Dekker, Annelot, additional, Gawor, Klara, additional, Westeneng, Henk-Jan, additional, Tazelaar, Gijs, additional, Eijk, Kristel van, additional, Kooyman, Maarten, additional, Byrne, Ross, additional, Doherty, Mark, additional, Heverin, Mark, additional, Khleifat, Ahmad Al, additional, Iacoangeli, Alfredo, additional, Shatunov, Aleksey, additional, Ticozzi, Nicola, additional, Cooper-Knock, Johnathan, additional, Smith, Bradley, additional, Gromicho, Marta, additional, Chandran, Siddharthan, additional, Pal, Suvankar, additional, Morrison, Karen, additional, Shaw, Pamela, additional, Hardy, John, additional, Orrell, Richard, additional, Sendtner, Michael, additional, Meyer, Thomas, additional, Basak, Nazli, additional, Kooi, Anneke van der, additional, Ratti, Antonia, additional, Fogh, Isabella, additional, Gellera, Cinzia, additional, Pinter, Guiseppe Lauria, additional, Corti, Stefania, additional, Cereda, Cristina, additional, Sproviero, Daisy, additional, D'Alfonso, Sandra, additional, Soraru, Gianni, additional, Siciliano, Gabriele, additional, Filosto, Massimiliano, additional, Padovani, Alessandro, additional, Chio, Adriano, additional, Calvo, Andrea, additional, Moglia, Cristina, additional, Brunetti, Maura, additional, Canosa, Antonio, additional, Grassano, Maurizio, additional, Beghi, Ettore, additional, Pupillo, Elisabetta, additional, Logroscino, Giancarlo, additional, Nefussy, Beatrice, additional, Osmanovic, Alma, additional, Nordin, Angelica, additional, Lerner, Yossef, additional, Zabari, Michal, additional, Gotkine, Marc, additional, Baloh, Robert, additional, Bell, Shaugn, additional, Vourc'h, Patrick, additional, Corcia, Philippe, additional, Couratier, Philippe, additional, Millecamps, Stephanie, additional, Meininger, Vincent, additional, Salachas, Francois, additional, Pardina, Jesus Mora, additional, Assialioui, Abdelilah, additional, Rojas-García, Ricardo, additional, Dion, Patrick, additional, Ross, Jay, additional, Ludolph, Albert, additional, Weishaupt, Jochen, additional, Brenner, David, additional, Freischmidt, Axel, additional, Bensimon, Gilbert, additional, Brice, Alexis, additional, Durr, Alexandra, additional, Payan, Christine, additional, Saker-Delye, Safa, additional, Wood, Nicholas, additional, Topp, Simon, additional, Rademakers, Rosa, additional, Tittmann, Lukas, additional, Lieb, Wolfgang, additional, Franke, Andre, additional, Ripke, Stephan, additional, Braun, Alice, additional, Kraft, Julia, additional, Whiteman, David, additional, Olsen, Catherine, additional, Uitterlinden, André, additional, Hofman, Albert, additional, Rietschel, Marcella, additional, Cichon, Sven, additional, Nöthen, Markus, additional, Amouyel, Philippe, additional, Traynor, Bryan, additional, Singleton, Andrew, additional, Neto, Miguel Mitne, additional, Cauchi, Ruben, additional, Ophoff, Roel, additional, Wiedau-Pazos, Martina, additional, Lomen-Hoerth, Catherine, additional, Deerlin, Vivianna Van, additional, Grosskreutz, Julian, additional, Rödiger, Annekathrin, additional, Jörk, Alexander, additional, Barthel, Tabea, additional, Theele, Erik, additional, Ilse, Berjamin, additional, Stubendorff, Beatrice, additional, Witte, Otto, additional, Steinbach, Robert, additional, Hübner, Christian, additional, Graff, Caroline, additional, Brylev, Lev, additional, Fominykh, Vera, additional, Demeshonok, Vera, additional, Ataulina, Anastasia, additional, Rogelj, Boris, additional, Koritnik, Blaž, additional, Zidar, Janez, additional, Ravnik-Glavač, Metka, additional, Glavač, Damjan, additional, Stević, Zorica, additional, Drory, Vivian, additional, Povedano, Mónica, additional, Blair, Ian, additional, Kiernan, Matthew, additional, Benyamin, Beben, additional, Henderson, Robert, additional, Furlong, Sarah, additional, Mathers, Susan, additional, McCombe, Pamela, additional, Needham, Merrilee, additional, Ngo, Shyuan, additional, Nicholson, Garth, additional, Pamphlett, Roger, additional, Rowe, Dominic, additional, Steyn, Frederik, additional, Williams, Kelly, additional, Mather, Karen, additional, Sachdev, Perminder, additional, Henders, Anjali, additional, Wallace, Leanne, additional, de Carvalho, Mamede, additional, Pinto, Susana, additional, Petri, Susanne, additional, Weber, Markus, additional, Rouleau, Guy, additional, Silani, Vincenzo, additional, Curtis, Charles, additional, Breen, Gerome, additional, Glass, Jonathan, additional, Brown, Robert, additional, Landers, John, additional, Shaw, Christopher, additional, Andersen, Peter, additional, Groen, Ewout, additional, Es, Michael van, additional, Pasterkamp, Jeroen, additional, Fan, Dongsheng, additional, Garton, Fleur, additional, McRae, Allan, additional, Smith, George Davey, additional, Gaunt, Tom, additional, Eberle, Michael, additional, Mill, Jonathan, additional, McLaughlin, Russell, additional, Hardiman, Orla, additional, Kenna, Kevin, additional, Wray, Naomi, additional, Tsai, Ellen, additional, Runz, Heiko, additional, Franke, Lude, additional, Al-Chalabi, Ammar, additional, Damme, Philip Van, additional, and Gaur, Nayana, additional
Published: 2021
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49. Autism-related dietary preferences mediate autism-gut microbiome associations

Author: Lorelle Nunn, Anne Masi, Paul M. Thompson, Peter M. Visscher, Mira Levis Frenk, Anjali K. Henders, Alexis Harun, Michaela Nothard, Jacob Gratten, Paul A. Dawson, Lachlan T. Strike, Cheryl Dissanayake, Jodie Leslie, David L. A. Wood, Margaret J. Wright, Gail A. Alvares, Claire Hafekost, Jessica L. Miller, Melanie Muniandy, Lauren P. Lawson, Chloe X. Yap, Allan F. McRae, Gerald Holtmann, Leanne Wallace, Katie L. McMahon, Rachel Grove, Helen Heussler, Valsamma Eapen, Restuadi Restuadi, Rachel Jellett, Nisha E. Mathew, Narelle K. Hansell, Tiana McLaren, Naomi R. Wray, Feroza Khan, Lutz Krause, Dominique Cleary, Helen Holdsworth, Gene W. Tyson, Greig I. de Zubicaray, and Andrew J. O. Whitehouse
Subjects: Stool consistency, Confounding, Biology, medicine.disease, behavioral disciplines and activities, Biobank, General Biochemistry, Genetics and Molecular Biology, Gut microbiome, Autism spectrum disorder, Metagenomics, mental disorders, medicine, Autism, Microbiome, Clinical psychology
Abstract: There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
Published: 2021
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50. Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics

Author: Iacoangeli, Alfredo, primary, Lin, Tian, additional, Al Khleifat, Ahmad, additional, Jones, Ashley R., additional, Opie-Martin, Sarah, additional, Coleman, Jonathan R.I., additional, Shatunov, Aleksey, additional, Sproviero, William, additional, Williams, Kelly L., additional, Garton, Fleur, additional, Restuadi, Restuadi, additional, Henders, Anjali K., additional, Mather, Karen A., additional, Needham, Merilee, additional, Mathers, Susan, additional, Nicholson, Garth A., additional, Rowe, Dominic B., additional, Henderson, Robert, additional, McCombe, Pamela A., additional, Pamphlett, Roger, additional, Blair, Ian P., additional, Schultz, David, additional, Sachdev, Perminder S., additional, Newhouse, Stephen J., additional, Proitsi, Petroula, additional, Fogh, Isabella, additional, Ngo, Shyuan T., additional, Dobson, Richard J.B., additional, Wray, Naomi R., additional, Steyn, Frederik J., additional, and Al-Chalabi, Ammar, additional
Published: 2020
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