{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:36:47Z","timestamp":1790811407191,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T00:00:00Z","timestamp":1588896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T00:00:00Z","timestamp":1588896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gene-environment interactions, by means of abnormal macromolecular intestinal adsorption, is one of the possible causes of autism spectrum disorders (ASD) predominantly in patients with gastrointestinal disorders. Pre-haptoglobin-2 (zonulin), encoded by the<jats:italic>Haptoglobin<\/jats:italic>(HP) allele-2 gene, enhances the intestinal permeability by modulation of intercellular tight junctions. The two alleles of<jats:italic>HP<\/jats:italic>,<jats:italic>HP1<\/jats:italic>and<jats:italic>HP2<\/jats:italic>, differ for 2 extra exons in<jats:italic>HP2<\/jats:italic>that result in exon duplication undetectable by classic genome-wide association studies. To evaluate the role of<jats:italic>HP2<\/jats:italic>in ASD pathogenesis and to set up a method to discriminate<jats:italic>HP<\/jats:italic>alleles, Italian subjects with ASD (n\u2009=\u2009398) and healthy controls (n\u2009=\u2009379) were genotyped by PCR analysis; subsequently, the PCR results were integrated with microarray genotypes (Illumina Human Omni 1S-8), obtained using a subset from the same subjects, and then we developed a computational method to predict<jats:italic>HP<\/jats:italic>alleles. On the contrary to our expectations, there was no association between<jats:italic>HP2<\/jats:italic>and ASD (P\u2009&gt;\u20090.05), and there was no significant allele association in subjects with ASD with or without gastrointestinal disorders (P\u2009&gt;\u20090.05). With the aid of bioinformatics analysis, from a window frame of ~2\u2009Mb containing 314 SNPs, we obtain imputation accuracy (r<jats:sup>2<\/jats:sup>) between 0.4 and 0.9 (median 0.7) and correct predictions were between 70% and 100% (median 90%). The conclusions endorse that enhanced intestinal permeability in subjects with ASD should not be imputed to<jats:italic>HP2<\/jats:italic>but to other members of the zonulin family and\/or to environmental factors.<\/jats:p>","DOI":"10.1038\/s41598-020-64679-w","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T10:03:33Z","timestamp":1588932213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assessment of haptoglobin alleles in autism spectrum disorders"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-1772","authenticated-orcid":false,"given":"Francesca Anna","family":"Cupaioli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3102-5150","authenticated-orcid":false,"given":"Ettore","family":"Mosca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-8666","authenticated-orcid":false,"given":"Chiara","family":"Magri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Gennarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Moscatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisabetta","family":"Raggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Landini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-5242","authenticated-orcid":false,"given":"Nadia","family":"Galluccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Villa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Bonfanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Renieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fallerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Minelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-5205","authenticated-orcid":false,"given":"Anna","family":"Marabotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-3939","authenticated-orcid":false,"given":"Luciano","family":"Milanesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-0261","authenticated-orcid":false,"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-5869","authenticated-orcid":false,"given":"Alessandra","family":"Mezzelani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,8]]},"reference":[{"key":"64679_CR1","first-page":"1","volume":"61","author":"Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention","year":"2012","unstructured":"Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders\u2013Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 61, 1\u201319 (2012).","journal-title":"MMWR Surveill Summ."},{"key":"64679_CR2","first-page":"569","volume":"67","author":"I Smaga","year":"2015","unstructured":"Smaga, I. et al. Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacol. Rep. 67, 569\u201380 (2015).","journal-title":"Depression, anxiety, schizophrenia and autism. Pharmacol. Rep."},{"key":"64679_CR3","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1124\/dmd.115.063826","volume":"43","author":"CS Rosenfeld","year":"2015","unstructured":"Rosenfeld, C. S. Microbiome Disturbances and Autism Spectrum Disorders. Drug Metab. Dispos. 43, 1557\u201371 (2015).","journal-title":"Drug Metab. Dispos."},{"key":"64679_CR4","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1097\/MPG.0b013e3181dcc4a5","volume":"51","author":"L de Magistris","year":"2010","unstructured":"de Magistris, L. et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J. Pediatr. Gastroenterol. Nutr. 51, 418\u201324 (2010).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"64679_CR5","doi-asserted-by":"crossref","unstructured":"de Magistris, L. et al. Antibodies against food antigens in patients with autistic spectrum disorders. Biomed. Res. Int. 729349 (2013).","DOI":"10.1155\/2013\/729349"},{"key":"64679_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-7-247","volume":"13","author":"JM Berg","year":"2012","unstructured":"Berg, J. M. & Geschwind, D. H. Autism genetics: searching for specificity and convergence. Genome Biol. 13, 247 (2012).","journal-title":"Genome Biol."},{"key":"64679_CR7","first-page":"11","volume":"16","author":"JB Adams","year":"2011","unstructured":"Adams, J. B., Johansen, L. J., Powell, L. D., Quig, D. & Rubin, R. A. Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 16, 11\u201322 (2011).","journal-title":"BMC Gastroenterol."},{"key":"64679_CR8","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1542\/peds.2009-1878D","volume":"125","author":"T Buie","year":"2010","unstructured":"Buie, T. et al. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics. 125, S19\u201329 (2010).","journal-title":"Pediatrics."},{"key":"64679_CR9","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1097\/HRP.0000000000000029","volume":"22","author":"EY Hsiao","year":"2014","unstructured":"Hsiao, E. Y. Gastrointestinal issues in autism spectrum disorder. Harv. Rev. Psychiatry. 22, 104\u201311 (2014).","journal-title":"Harv. Rev. Psychiatry."},{"key":"64679_CR10","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1007\/s00204-016-1794-8","volume":"91","author":"P Akbari","year":"2017","unstructured":"Akbari, P. et al. The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins. Arch. Toxicol. 91, 1007\u201329 (2017).","journal-title":"Arch. Toxicol."},{"key":"64679_CR11","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1096\/fj.10-158972","volume":"25","author":"SE Goldblum","year":"2011","unstructured":"Goldblum, S. E. et al. The active Zot domain (aa 288\u2013293) increases ZO-1 and myosin 1C serine\/threonine phosphorylation, alters interaction between ZO-1 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation. FASEB J. 25, 144\u201358 (2011).","journal-title":"FASEB J."},{"key":"64679_CR12","doi-asserted-by":"publisher","first-page":"16799","DOI":"10.1073\/pnas.0906773106","volume":"106","author":"A Tripathi","year":"2009","unstructured":"Tripathi, A. et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc. Natl. Acad. Sci. USA 106, 16799\u2013804 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"64679_CR13","doi-asserted-by":"publisher","first-page":"4435","DOI":"10.1242\/jcs.113.24.4435","volume":"113","author":"W Wang","year":"2000","unstructured":"Wang, W., Uzzau, S., Goldblum, S. E. & Fasano, A. Human zonulin, a potential modulator of intestinal tight junctions. J. Cell Sci. 113, 4435\u201340 (2000).","journal-title":"J. Cell Sci."},{"key":"64679_CR14","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.trstmh.2008.04.010","volume":"102","author":"IK Quaye","year":"2008","unstructured":"Quaye, I. K. Haptoglobin, inflammation and disease. Trans. R. Soc. Trop. Med. Hyg. 102, 735\u201342 (2008).","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"64679_CR15","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1111\/j.1365-2249.1991.tb05666.x","volume":"83","author":"JG Raynes","year":"1991","unstructured":"Raynes, J. G., Eagling, S. & McAdam, K. P. Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6. Clin. Exp. Immunol. 83, 488\u201391 (1991).","journal-title":"Clin. Exp. Immunol."},{"key":"64679_CR16","doi-asserted-by":"publisher","first-page":"5875","DOI":"10.1073\/pnas.80.19.5875","volume":"80","author":"F Yang","year":"1983","unstructured":"Yang, F., Brune, J. L., Baldwin, W. D., Barnett, D. R. & Bowman, B. H. Identification and characterization of human haptoglobin cDNA. Proc. Natl. Acad. Sci. USA 80, 5875\u20139 (1983).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"64679_CR17","doi-asserted-by":"publisher","first-page":"3693","DOI":"10.1182\/blood.V98.13.3693","volume":"98","author":"M Melamed-Frank","year":"2001","unstructured":"Melamed-Frank, M. et al. Structure-function analysis of the antioxidant properties of haptoglobin. Blood. 98, 3693\u20138 (2001).","journal-title":"Blood."},{"key":"64679_CR18","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cccn.2004.03.016","volume":"345","author":"H Van Vlierberghe","year":"2004","unstructured":"Van Vlierberghe, H., Langlois, M. & Delanghe, J. Haptoglobin polymorphisms and iron homeostasis in health and in disease. Clin. Chim. Acta. 345, 35\u201342 (2004).","journal-title":"Clin. Chim. Acta."},{"key":"64679_CR19","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/218736a0","volume":"218","author":"JA Black","year":"1968","unstructured":"Black, J. A. & Dixon, G. H. Amino-acid sequence of alpha chains of human haptoglobins. Nature. 218, 736\u201341 (1968).","journal-title":"Nature."},{"key":"64679_CR20","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1182\/blood-2008-08-174466","volume":"113","author":"PW Buehler","year":"2009","unstructured":"Buehler, P. W. et al. Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification. Blood. 113, 2578\u201386 (2009).","journal-title":"Blood."},{"key":"64679_CR21","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1093\/clinchem\/42.10.1589","volume":"42","author":"MR Langlois","year":"1996","unstructured":"Langlois, M. R. & Delanghe, J. R. Biological and clinical significance of haptoglobin polymorphis in humans. Clin. Chem. 42, 1589\u2013600 (1996).","journal-title":"Clin. Chem."},{"key":"64679_CR22","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.cca.2010.12.006","volume":"412","author":"V Napolioni","year":"2011","unstructured":"Napolioni, V., Giann\u00ec, P., Carpi, F. M., Concetti, F. & Lucarini, N. Haptoglobin (HP) polymorphisms and human longevity: a cross-sectional association study in a Central Italy population. Clin. Chim. Acta. 412, 574\u20137 (2011).","journal-title":"Clin. Chim. Acta."},{"key":"64679_CR23","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1089\/ars.2009.2793","volume":"12","author":"AP Levy","year":"2010","unstructured":"Levy, A. P. et al. Haptoglobin: basic and clinical aspects. Antioxid. Redox Signal. 12, 293\u2013304 (2010).","journal-title":"Antioxid. Redox Signal."},{"key":"64679_CR24","doi-asserted-by":"publisher","first-page":"S282","DOI":"10.1002\/pmic.200500404","volume":"6","author":"EJ Pav\u00f3n","year":"2006","unstructured":"Pav\u00f3n, E. J. et al. Proteomic analysis of plasma from patients with systemic lupus erythematosus: increased presence of haptoglobin alpha2 polypeptide chains over the alpha1 isoforms. Proteomics. 6, S282\u201392 (2006).","journal-title":"Proteomics."},{"key":"64679_CR25","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s00421-009-1048-z","volume":"106","author":"L Dayan","year":"2009","unstructured":"Dayan, L. et al. Haptoglobin genotype and endothelial function in diabetes mellitus: a pilot study. Eur. J. Appl. Physiol. 106, 639\u201344 (2009).","journal-title":"Eur. J. Appl. Physiol."},{"key":"64679_CR26","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1749-6632.2012.06538.x","volume":"1258","author":"A Fasano","year":"2012","unstructured":"Fasano, A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann. N. Y. Acad. Sci. 1258, 25\u201333 (2012).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"64679_CR27","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fendo.2018.00022","volume":"9","author":"L Scheffler","year":"2018","unstructured":"Scheffler, L. et al. Widely used commercial ELISA does not detect precursor of Haptoglobin2, but recognizes Properdin as a potential second member of the Zonulin family. Front. Endocrinol. (Lausanne). 9, 22 (2018).","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"64679_CR28","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/j.cgh.2012.08.012","volume":"10","author":"A Fasano","year":"2012","unstructured":"Fasano, A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 10, 1096\u2013100 (2012).","journal-title":"Clin Gastroenterol Hepatol."},{"key":"64679_CR29","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.jpeds.2017.04.004","volume":"188","author":"E Esnafoglu","year":"2017","unstructured":"Esnafoglu, E. et al. Increased serum Zonulin levels as an intestinal permeability marker in autistic subjects. J. Pediatr. 188, 240\u201344 (2017).","journal-title":"J. Pediatr."},{"key":"64679_CR30","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.bbi.2018.03.025","volume":"70","author":"DR Rose","year":"2018","unstructured":"Rose, D. R. et al. Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain Behav. Immun. 70, 354\u201368 (2018).","journal-title":"Brain Behav. Immun."},{"key":"64679_CR31","unstructured":"Lord, C. et al. ADOS-2\u2014Autism Diagnostic Observation Schedule, 2nd ed.; Lord, C. & Rutter, M., Eds.; Western Psychological Services: Torrance, CA, USA (2012)."},{"key":"64679_CR32","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/BF02172145","volume":"24","author":"C Lord","year":"1994","unstructured":"Lord, C., Rutter, M. & Le Couteur, A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J. Autism Dev. Disord. 1994 24, 659\u201385 (1994).","journal-title":"J. Autism Dev. Disord. 1994"},{"key":"64679_CR33","unstructured":"Sheehan, D. V. et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry. 59 Suppl 20, 22\u201333. quiz 34\u201357 (1998)."},{"key":"64679_CR34","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. Mini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189\u201398 (1975).","journal-title":"J. Psychiatr. Res."},{"key":"64679_CR35","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1093\/clinchem\/48.9.1377","volume":"48","author":"W Koch","year":"2002","unstructured":"Koch, W. et al. Genotyping of the common haptoglobin Hp 1\/2 polymorphism based on PCR. Clin. Chem. 48, 1377\u201382 (2002).","journal-title":"Clin. Chem."},{"key":"64679_CR36","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0015-0282(99)00210-1","volume":"72","author":"N Bottini","year":"1999","unstructured":"Bottini, N. et al. Haptoglobin genotype and natural fertility in humans. Fertil. Steril. 72, 293\u20136 (1999).","journal-title":"Fertil. Steril."},{"key":"64679_CR37","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/tpj.2015.90","volume":"17","author":"E Sacchetti","year":"2017","unstructured":"Sacchetti, E. et al. The GRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis. Pharmacogenomics J. 17, 146\u201354 (2017).","journal-title":"Pharmacogenomics J."},{"key":"64679_CR38","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1086\/521987","volume":"81","author":"SR Browning","year":"2007","unstructured":"Browning, S. R. & Browning, B. L. Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am. J Hum. Genet. 81, 1084\u201397 (2007).","journal-title":"Am. J Hum. Genet."},{"key":"64679_CR39","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.ajhg.2015.11.020","volume":"98","author":"BL Browning","year":"2016","unstructured":"Browning, B. L. & Browning, S. R. Genotype Imputation with Millions of Reference Samples. Am. J. Hum. Genet. 98, 116\u201326 (2016).","journal-title":"Am. J. Hum. Genet."},{"key":"64679_CR40","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/icb.1971.58","volume":"49","author":"CJ Brackenridge","year":"1971","unstructured":"Brackenridge, C. J. A sex-dependent difference in the haptoglobin distributions of some Australian urban population samples, with a note on the method of Haldane for estimating the significance of the logarithm of a ratio of frequencies. J. Exp. Biol. Med. Sci. 49, 525\u20139 (1971).","journal-title":"J. Exp. Biol. Med. Sci."},{"key":"64679_CR41","doi-asserted-by":"publisher","first-page":"e27321","DOI":"10.4161\/tisb.27321","volume":"1","author":"T Vanuytsel","year":"2013","unstructured":"Vanuytsel, T., Vermeire, S. & Cleynen, I. The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers. 1, e27321 (2013).","journal-title":"Tissue Barriers."},{"key":"64679_CR42","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/j.1751-553X.2007.00898.x","volume":"29","author":"K Carter","year":"2007","unstructured":"Carter, K. & Worwood, M. Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases. Int. J. Lab. Hematol. 29, 92\u2013110 (2007).","journal-title":"Int. J. Lab. Hematol."},{"key":"64679_CR43","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1159\/000154130","volume":"43","author":"H Zhao","year":"1993","unstructured":"Zhao, H., Zhang, G., Duan, Y. & Yu, S. Haptoglobin types in Chinese ethnic groups. Hum. Hered. 43, 131\u20133 (1993).","journal-title":"Hum. Hered."},{"key":"64679_CR44","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1016\/j.bbrc.2006.04.018","volume":"344","author":"J Wei","year":"2006","unstructured":"Wei, J. & Hemmings, G. P. A further study of a possible locus for schizophrenia on the X chromosome. Biochem. Biophys. Res. Commun. 344, 1241\u20135 (2006).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"64679_CR45","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1038\/mp.2010.54","volume":"16","author":"A Piton","year":"2011","unstructured":"Piton, A. et al. Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol. Psychiatry. 16, 867\u201380 (2011).","journal-title":"Mol. Psychiatry."},{"key":"64679_CR46","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/ejhg.2012.243","volume":"21","author":"A Piton","year":"2013","unstructured":"Piton, A. et al. Analysis of the effects of rare variants on splicing identifies alterations in GABAA receptor genes in autism spectrum disorder individuals. Eur. J. Hum. Genet. 21, 749\u201356 (2013).","journal-title":"J. Hum. Genet."},{"key":"64679_CR47","doi-asserted-by":"publisher","first-page":"e24585","DOI":"10.1371\/journal.pone.0024585","volume":"6","author":"BL Williams","year":"2011","unstructured":"Williams, B. L. et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. Plos One. 6, e24585 (2011).","journal-title":"Plos One."},{"key":"64679_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-017-0242-1","volume":"5","author":"F Strati","year":"2017","unstructured":"Strati, F. et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 5, 24 (2017).","journal-title":"Microbiome."},{"key":"64679_CR49","doi-asserted-by":"publisher","first-page":"333","DOI":"10.23736\/S1121-421X.18.02493-5","volume":"64","author":"D Campion","year":"2018","unstructured":"Campion, D., Ponzo, P., Alessandria, C., Saracco, G. M. & Balzola, F. The role of microbiota in autism spectrum disorders. Minerva Gastroenterol. Dietol. 64, 333\u201350 (2018).","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"64679_CR50","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1007\/s00248-018-1176-2","volume":"76","author":"J Pulikkan","year":"2018","unstructured":"Pulikkan, J. et al. Gut microbial dysbiosis in Indian children with autism spectrum disorders. Microb. Ecol. 76, 1102\u201314 (2018).","journal-title":"Microb. Ecol."},{"key":"64679_CR51","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1007\/s10620-019-05646-y","volume":"64","author":"F Valitutti","year":"2019","unstructured":"Valitutti, F. & Fasano, A. Breaking down barriers: how understanding celiac disease pathogenesis informed the development of novel treatments. Dig. Dis. Sci. 64, 1748\u201358 (2019).","journal-title":"Dig. Dis. Sci."},{"key":"64679_CR52","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1097\/FBP.0000000000000428","volume":"29","author":"P Roman","year":"2018","unstructured":"Roman, P., Rueda-Ruzafa, L., Cardona, D. & Cortes-Rodr\u00edguez, A. Gut-brain axis in the executive function of austism spectrum disorder. Behav. Pharmacol. 29, 654\u201363 (2018).","journal-title":"Behav. Pharmacol."},{"key":"64679_CR53","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/ajmg.b.32567","volume":"174","author":"R Alam","year":"2017","unstructured":"Alam, R., Abdolmaleky, H. M. & Zhou, J. R. Microbiome, inflammation, epigenetic alterations, and mental diseases. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 174, 651\u201360 (2017).","journal-title":"Am. J. Med. Genet. B. Neuropsychiatr. Genet."},{"key":"64679_CR54","doi-asserted-by":"publisher","first-page":"E203","DOI":"10.3390\/toxins9070203","volume":"9","author":"B De Santis","year":"2017","unstructured":"De Santis, B. et al. Study on the association among mycotoxins and other variables in children with autism. Toxins (Basel). 9, E203 (2017).","journal-title":"Toxins (Basel)."},{"key":"64679_CR55","first-page":"1","volume":"10","author":"B De Santis","year":"2017","unstructured":"De Santis, B. et al. Role of mycotoxins in the pathobiology of autism: A first evidence. Nutr. Neurosci. 10, 1\u201313 (2017).","journal-title":"Nutr. Neurosci."},{"key":"64679_CR56","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fcimb.2018.00060","volume":"8","author":"WP Liew","year":"2018","unstructured":"Liew, W. P. & Mohd-Redzwan, S. Mycotoxin: its impact on gut health and microbiota. Front Cell Infect Microbiol. 8, 60 (2018).","journal-title":"Front Cell Infect Microbiol."},{"key":"64679_CR57","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.jacc.2013.04.079","volume":"62","author":"LE Cahill","year":"2013","unstructured":"Cahill, L. E. et al. Currently available versions of genome-wide association studies cannot be used to query the common haptoglobin copy number variant. J. Am. Coll. Cardiol. 62, 860\u20131 (2013).","journal-title":"J. Am. Coll. Cardiol."},{"key":"64679_CR58","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/ng.3510","volume":"48","author":"LM Boettger","year":"2016","unstructured":"Boettger, L. M. et al. Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels. Nat Genet. 48, 359\u201366 (2016).","journal-title":"Nat Genet."},{"key":"64679_CR59","doi-asserted-by":"publisher","first-page":"e0210728","DOI":"10.1371\/journal.pone.0210728","volume":"14","author":"M Ajamian","year":"2019","unstructured":"Ajamian, M., Steer, D., Rosella, G. & Gibson, P. R. Serum zonulin as a marker of intestinal mucosal barrier function: may not be what it seems. Plos One. 14, e0210728 (2019).","journal-title":"Plos One."}],"updated-by":[{"DOI":"10.1038\/s41598-023-33293-x","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64679-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64679-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64679-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T20:58:12Z","timestamp":1696107492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64679-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,8]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["64679"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-64679-w","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41598-023-33293-x","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,8]]},"assertion":[{"value":"11 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2023","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-023-33293-x","URL":"https:\/\/doi.org\/10.1038\/s41598-023-33293-x","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7758"}}