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Associations between autistic-like traits and polymorphisms in NFKBIL1

Published online by Cambridge University Press:  04 June 2019

Nina Strenn Open the ORCID record for Nina Strenn [Opens in a new window] ,
Daniel Hovey ,
Lina Jonsson ,
Henrik Anckarsäter ,
Sebastian Lundström ,
Paul Lichtenstein  and
Agneta Ekman
Nina Strenn*
Affiliation:
Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Daniel Hovey
Affiliation:
Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Lina Jonsson
Affiliation:
Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Henrik Anckarsäter
Affiliation:
Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Gothenburg, Sweden
Sebastian Lundström
Affiliation:
Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Gothenburg, Sweden Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden
Paul Lichtenstein
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Agneta Ekman
Affiliation:
Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
*
Author for correspondence: Nina Strenn, Email: [email protected]
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Abstract

Objective:

The immune system has been suggested to be associated with neuropsychiatric disorders; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NF-κB) have been reported in individuals with autism spectrum disorder (ASD). The aim of this study was to investigate possible associations between autistic-like traits (ALTs) and single nucleotide polymorphisms (SNPs) in NFKB1 (encoding a subunit of the NF-κB protein complex) and NF-κB inhibitor-like protein 1 (NFKBIL1).

Methods:

The study was conducted in a cohort from the general population: The Child and Adolescent Twin Study in Sweden (CATSS, n = 12 319, 9–12 years old). The subjects were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory. Five SNPs within the two genes were genotyped (NFKBIL1: rs2857605, rs2239707, rs2230365 and rs2071592; NFKB1: rs4648022).

Results:

We found significant associations for two SNPs in NFKBIL1: rs2239707 showed a significant distribution of genotype frequencies in the case-control analysis both for all individuals combined and in boys only, and rs2230365 was significantly associated with the ALTs-module language impairment in boys only. Furthermore, we found nominal association in the case-control study for rs2230365, replicating earlier association between this SNP and ASD in an independent genome-wide association study.

Conclusion:

The shown associations between polymorphisms in NFKBIL1 and ALTs are supporting an influence of the immune system on neuropsychiatric symptoms.

Keywords

autistic disordersimmune systempolymorphismsingle nucleotide
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 31 , Issue 4 , August 2019 , pp. 220 - 229
Copyright
© Scandinavian College of Neuropsychopharmacology 2019 

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References

Aberg, KA, Liu, Y, Bukszár, J, McClay, JL, Khachane, AN, Andreassen, OA, Blackwood, D, Corvin, A, Djurovic, S, Gurling, H, Ophoff, R, Pato, CN, Pato, MT, Riley, B, Webb, T, Kendler, K, O’Donovan, M, Craddock, N, Kirov, G, Owen, M, Rujescu, D, St Clair, D, Werge, T, Hultman, CM, Delisi, LE, Sullivan, P and Van Den Oord, EJ (2013) A comprehensive family-based replication study of schizophrenia genes. JAMA Psychiatry 70(6), 573–581.CrossRefGoogle ScholarPubMed
Albertella, MR and Campbell, RD (1994) Characterization of a novel gene in the human major histocompatibility complex that encodes a potential new member of the I kappa B family of proteins. Human Molecular Genetics 3(5), 793–799.CrossRefGoogle ScholarPubMed
Al-Haddad, BJS, Jacobsson, B, Chabra, S, Modzelewska, D, Olson, EM, Bernier, R, Enquobahrie, DA, Hagberg, H, Östling, S, Rajagopal, L, Adams Waldorf, KM and Sengpiel, V (2019) Long-term risk of neuropsychiatric disease after exposure to infection in utero. JAMA Psychiatry 91985, 1–9.Google Scholar
American Psychiatric Association. Diagnostic and statistical manual of mental disorders 4th Edn (DSM-IV). Washington, DC: American Psychiatric Association; 1994.Google Scholar
An, J, Nakajima, T, Shibata, H, Arimura, T, Yasunami, M and Kimura, A (2013) A novel link of HLA locus to the regulation of immunity and infection: NFKBIL1 regulates alternative splicing of human immune-related genes and influenza virus M gene. Journal of Autoimmunity 47, 25–33.CrossRefGoogle ScholarPubMed
Anckarsäter, H, Lundström, S, Kollberg, L, Kerekes, N, Palm, C, Carlström, E, Långström, N, Magnusson, PKE, Halldner, L, Bölte, S, Gillberg, C, Gumpert, C, Råstam, M and Lichtenstein, P (2011) The child and adolescent twin study in Sweden (CATSS). Twin Research and Human Genetics 14(6), 495–508.CrossRefGoogle Scholar
Anney, R, Klei, L, Pinto, D, Regan, R, Conroy, J, Magalhaes, TR, Correia, C, Abrahams, BS, Sykes, N, Pagnamenta, AT, Almeida, J, Bacchelli, E, Bailey, AJ, Baird, G, Battaglia, A, Berney, T, Bolshakova, N, Bölte, S, Bolton, PF, Bourgeron, T, Brennan, S, Brian, J, Carson, AR, Casallo, G, Casey, J, Chu, SH, Cochrane, L, Corsello, C, Crawford, EL, Crossett, A, Dawson, G, de Jonge, M, Delorme, R, Drmic, I, Duketis, E, Duque, F, Estes, A, Farrar, P, Fernandez, BA, Folstein, SE, Fombonne, E, Freitag, CM, Gilbert, J, Gillberg, C, Glessner, JT, Goldberg, J, Green, J, Guter, SJ, Hakonarson, H, Heron, EA, Hill, M, Holt, R, Howe, JL, Hughes, G, Hus, V, Igliozzi, R, Kim, C, Klauck, SM, Kolevzon, A, Korvatska, O, Kustanovich, V, Lajonchere, CM, Lamb, JA, Laskawiec, M, Leboyer, M, Le Couteur, A, Leventhal, BL, Lionel, AC, Liu, XQ, Lord, C, Lotspeich, L, Lund, SC, Maestrini, E, Mahoney, W, Mantoulan, C, Marshall, CR, McConachie, H, McDougle, CJ, McGrath, J, McMahon, WM, Melhem, NM, Merikangas, A, Migita, O, Minshew, NJ, Mirza, GK, Munson, J, Nelson, SF, Noakes, C, Noor, A, Nygren, G, Oliveira, G, Papanikolaou, K, Parr, JR, Parrini, B, Paton, T, Pickles, A, Piven, J, Posey, DJ, Poustka, A, Poustka, F, Prasad, A, Ragoussis, J, Renshaw, K, Rickaby, J, Roberts, W, Roeder, K, Roge, B, Rutter, ML, Bierut, LJ, Rice, JP, Salt, J, Sansom, K, Sato, D, Segurado, R, Senman, L, Shah, N, Sheffield, VC, Soorya, L, Sousa, I, Stoppioni, V, Strawbridge, C, Tancredi, R, Tansey, K, Thiruvahindrapduram, B, Thompson, AP, Thomson, S, Tryfon, A, Tsiantis, J, van Engeland, H, Vincent, JB, Volkmar, F, Wallace, S, Wang, K, Wang, Z, Wassink, TH, Wing, K, Wittemeyer, K, Wood, S, Yaspan, BL, Zurawiecki, D, Zwaigenbaum, L, Betancur, C, Buxbaum, JD, Cantor, RM, Cook, EH, Coon, H, Cuccaro, ML, Gallagher, L, Geschwind, DH, Gill, M, Haines, JL, Miller, J, Monaco, AP, Nurnberger, JI, Paterson, AD, Pericak-Vance, MA, Schellenberg, GD, Scherer, SW, Sutcliffe, JS, Szatmari, P, Vicente, AM, Vieland, VJ, Wijsman, EM, Devlin, B, Ennis, S and Hallmayer, J (2010) A genome-wide scan for common alleles affecting risk for autism. Human Molecular Genetics 19(20), 4072–4082.CrossRefGoogle ScholarPubMed
Ashwood, P, Krakowiak, P, Hertz-Picciotto, I, Hansen, R, Pessah, IN and Van de Water, J (2011a) Altered T cell responses in children with autism. Brain, Behavior, and Immunity 25(5), 840–849.CrossRefGoogle ScholarPubMed
Ashwood, P, Krakowiak, P, Hertz-Picciotto, I, Hansen, R, Pessah, IN and Van de Water, J (2011b) Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. Journal of Neuroimmunology 232(1–2), 196–199.CrossRefGoogle ScholarPubMed
Atladottir, HO, Henriksen, TB, Schendel, DE and Parner, ET (2012) Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics 130(6), e1447–e1454.CrossRefGoogle Scholar
Barrett, JC, Fry, B, Maller, J and Daly, MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2), 263–265.CrossRefGoogle ScholarPubMed
Boodhoo, A, Wong, AM-L, Williamson, D, Voon, D, Lee, S, Allcock, RJN and Price, P (2004) A promotor polymorphism in the central MHC gene, IKBL, influences the binding of transcription factors USF1 and E47 on disease-associated haplotypes. Gene Expression 12, 1–11.CrossRefGoogle Scholar
Border, R, Johnson, EC, Evans, LM, Smolen, A, Berley, N, Sullivan, PF and Keller, MC (2019) No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. The American Journal of Psychiatry (July): 1–12. doi: 10.1176/appi.ajp.2018.18070881 Google ScholarPubMed
Boulanger, LM (2009) Immune proteins in brain development and synaptic plasticity. Neuron 64(1), 93–109.CrossRefGoogle ScholarPubMed
Bralten, J, Van Hulzen, KJ, Martens, MB, Galesloot, TE, Arias Vasquez, A, Kiemeney, LA, Buitelaar, JK, Muntjewerff, JW, Franke, B and Poelmans, G (2018) Autism spectrum disorders and autistic traits share genetics and biology. Molecular Psychiatry 23(5), 1205–1212.CrossRefGoogle ScholarPubMed
Braunschweig, D, Krakowiak, P, Duncanson, P, Boyce, R, Hansen, RL, Ashwood, P, Hertz-Picciotto, I, Pessah, IN and Van De Water, J (2013) Autism-specific maternal autoantibodies recognize critical proteins in developing brain. Translational Psychiatry. 3(7), e277–e279.CrossRefGoogle ScholarPubMed
Brown, AS, Sourander, A, Hinkka-Yli-Salomäki, S, McKeague, IW, Sundvall, J and Surcel, HM (2014) Elevated maternal C-reactive protein and autism in a national birth cohort. Molecular Psychiatry 19(2), 259–264.CrossRefGoogle Scholar
Cardon, LR, Smith, SD, Fulker, DW, Kimberling, WJ, Pennington, BF and DeFries, JC (1994) Quantitative trait locus for reading disability on chromosome 6. Science 266(5183), 276–279.CrossRefGoogle ScholarPubMed
Castiblanco, J and Anaya, J-M (2008) The IkappaBL gene polymorphism influences risk of acquiring systemic lupus erythematosus and Sjögren’s syndrome. Human Immunology 69(1), 45–51.CrossRefGoogle ScholarPubMed
Cerhan, JR, Liu-Mares, W, Fredericksen, ZS, Novak, AJ, Cunningham, JM, Kay, NE, Dogan, A, Liebow, M, Wang, AH, Call, TG, Habermann, TM, Ansell, SM and Slager, SL (2008) Genetic variation in tumor necrosis factor and the nuclear factor-κB canonical pathway and risk of non-Hodgkin’s lymphoma. Cancer Epidemiology, Biomarkers & Prevention 17(11), 3161–3169.CrossRefGoogle ScholarPubMed
Chen, R, Davydov, EV, Sirsota, M and Butte, AJ (2010) Non-synonymous and synonymous coding SNPS show similar likelihood and effect size of human disease association. PLoS One 5(10), 1–6.CrossRefGoogle ScholarPubMed
Chen, Y, Shen, C, Guha, D, Ding, M, Kulich, S, Ashimkhanova, A, Rinaldo, C, Seaberg, E, Margolick, JB, Stosor, V, Mart�nez-Maza, O and Gupta, P (2016) Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV. BMC Infectious Diseases 16(1), 1–12.CrossRefGoogle ScholarPubMed
Chess, S (1971) Autism in children with congenital rubella. Journal of Autism and Childhood Schizophrenia 1(1), 33–47.CrossRefGoogle ScholarPubMed
Clancy, RM, Marion, MC, Kaufman, KM, Ramos, PS, Adler, A, Harley, JB, Langefeld, CD and Buyon, JP (2010) Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus. Arthritis & Rheumatology 62(11), 3415–3424.CrossRefGoogle Scholar
Comi, AM, Zimmerman, AW, Frye, VH, Law, PA and Peeden, JN (1999) Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. Journal of Child Neurology 14(6), 388–394.CrossRefGoogle ScholarPubMed
Cooper, DN (2010) Functional intronic polymorphisms: buried treasure awaiting discovery within our genes. Human Genomics 4(5), 284–288.CrossRefGoogle ScholarPubMed
Courchesne, E, Mouton, PR, Calhoun, ME, Semendeferi, K, Ahrens-Barbeau, C, Hallet, MJ, Barnes, CC and Pierce, K (2011) Neuron number and size in prefrontal cortex of children with autism. The Journal of the American Medical Association 306(18), 2001–2010.CrossRefGoogle ScholarPubMed
Crampton, SJ and O’Keeffe, GW (2013) NF-κB: emerging roles in hippocampal development and function. The International Journal of Biochemistry & Cell Biology 45(8), 1821–1824.CrossRefGoogle ScholarPubMed
Croonenberghs, J, Deboutte, D and Maes, M (2002) Activation of the inflammatory response system in autism. Neuropsychobiology 45, 1–6.CrossRefGoogle ScholarPubMed
Enstrom, AM, Lit, L, Onore, CE, Gregg, JP, Hansen, RL, Pessah, IN, Hertz-Picciotto, I, Van de Water, JA, Sharp, FR and Ashwood, P (2009) Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain, Behavior, and Immunity 23(1), 124–133.CrossRefGoogle ScholarPubMed
Fernando, MMA, Stevens, CR, Walsh, EC, De Jager, PL, Goyette, P, Plenge, RM, Vyse, TJ and Rioux, JD (2008) Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genetics 4(4), e1000024. doi: 10.1371/journal.pgen.1000024 CrossRefGoogle ScholarPubMed
Garbett, K, Ebert, PJ, Mitchell, A, Lintas, C, Manzi, B, Mirnics, K and Persico, AM (2008) Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiology of Disease 30(3), 303–311.CrossRefGoogle ScholarPubMed
Gesundheit, B, Rosenzweig, JP, Naor, D, Lerer, B, Zachor, DA, Procházka, V, Melamed, M, Kristt, DA, Steinberg, A, Shulman, C, Hwang, P, Koren, G, Walfisch, A, Passweg, JR, Snowden, JA, Tamouza, R, Leboyer, M, Farge-Bancel, D and Ashwood, P (2013) Immunological and autoimmune considerations of autism spectrum disorders. Journal of Autoimmunity 44, 1–7.CrossRefGoogle ScholarPubMed
Gonzalez, S, Gupta, J, Villa, E, Mallawaarachchi, I, Rodriguez, M, Ramirez, M, Zavala, J, Armas, R, Dassori, A, Contreras, J, Flores, D, Jerez, A, Ontiveros, A, Nicolini, H and Escamilla, M (2016) Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort. Bipolar Disorder 18(6), 520–527.CrossRefGoogle Scholar
Gough, SCL and Simmonds, MJ (2007) The HLA region and autoimmune disease: associations and mechanisms of action. Current Genomics 8(7), 453–465.Google ScholarPubMed
Greetham, D, Ellis, CD, Mewar, D, Fearon, U, an Ultaigh, SN, Veale, DJ, Guesdon, F and Wilson, AG (2007) Functional characterization of NF-kappaB inhibitor-like protein 1 (NFkappaBIL1), a candidate susceptibility gene for rheumatoid arthritis. Human Molecular Genetics 16(24), 3027–3036.CrossRefGoogle Scholar
Grove, J, Ripke, S, Als, TD, Mattheisen, M, Walters, RK, Won, H, Pallesen, J, Agerbo, E, Andreassen, OA, Anney, R, Awashti, S, Belliveau, R, Bettella, F, Buxbaum, JD, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Cerrato, F, Dellenvall, K, Chambert, K, Christensen, JH, Churchhouse, C, Demontis, D, De Rubeis, S, Devlin, B, Djurovic, S, Dumont, AL, Goldstein, JI, Hansen, CS, Hauberg, ME, Hollegaard, MV, Hope, S, Howrigan, DP, Huang, H, Hultman, CM, Klei, L, Maller, J, Martin, J, Martin, AR, Moran, JL, Nyegaard, M, Nærland, T, Palmer, DS, Palotie, A, Pedersen, CB, Pedersen, MG, DPoterba, T, Poulsen, JB, Pourcain, BS, Reichert, J, Qvist, P, Rehnström, K, Reichenberg, A, Robinson, EB, Roeder, K, Roussos, P, Saemundsen, E, Sandin, S, Satterstrom, FK, Smith, GD, Stefansson, H, Steinberg, S, Stevens6, CR, Sullivan, PF, Turley, P, Walters, GB, Xu, X, Consortium ASDW.G. of the P.G., BUPGEN, Consortium MDDW.G. of the P.G., Team MR, Stefansson, K, Geschwind, DH, Nordentoft, M, Hougaard, DM, Werge, T, Mors, O, Mortensen, PB, Neale, BM, Daly, MJ and Børglum, AD (2019) Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics 51, 431–444.CrossRefGoogle ScholarPubMed
Guerini, FR, Bolognesi, E, Chiappedi, M, De Silvestri, A, Ghezzo, A, Zanette, M, Rusconi, B, Manca, S, Sotgiu, S, Agliardi, C and Clerici, M (2011) HLA polymorphisms in Italian children with autism spectrum disorders: results of a family based linkage study. Journal of Neuroimmunology 230(1–2), 135–142.CrossRefGoogle ScholarPubMed
Gutierrez, H (2005) NF- B signalling regulates the growth of neural processes in the developing PNS and CNS. Development 132(7), 1713–1726.CrossRefGoogle ScholarPubMed
Hannelius, U, Gherman, L, Makela, VV, Lindstedt, A, Zucchelli, M, Lagerberg, C, Tybring, G, Kere, J and Lindgren, CM (2007) Large-scale zygosity testing using single nucleotide polymorphisms. Twin Research and Human Genetics 10(4), 604–625.CrossRefGoogle ScholarPubMed
Hansson, SL, Röjvall, AS, Rastam, M, Gillberg, C, Gillberg, C and Anckarsäter, H (2005) Psychiatric telephone interview with parents for screening of childhood autism - Tics, attention-deficit hyperactivity disorder and other comorbidities (A-TAC): preliminary reliability and validity. British Journal of Psychiatry 187(September), 262–267.CrossRefGoogle ScholarPubMed
Hunt, R, Sauna, ZE, Ambudkar, SV, Gottesman, MM and Kimchi-Sarfaty, C (2009) Silent (Synonymous) SNPs: should we care about them? Methods in Molecular Biology 578(1), 23–39.CrossRefGoogle Scholar
Hutton, J (2016) Does rubella cause autism: a 2015 reappraisal? Frontiers in Human Neuroscience 10(February), 1–15.CrossRefGoogle ScholarPubMed
Jacquemont, S, Coe, BP, Hersch, M, Duyzend, MH, Krumm, N, Bergmann, S, Beckmann, JS, Rosenfeld, JA and Eichler, EE (2014) A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. American Journal of Human Genetics 94(3), 415–425.CrossRefGoogle Scholar
Kimchi-Sarfaty, C, Oh, JM, Kim, IW, Sauna, ZE, Calcagno, AM, Ambudkar, SV and Gottesman, MM (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315(5811), 525–528.CrossRefGoogle ScholarPubMed
Lai, MC, Lombardo, MV and Baron-Cohen, S (2014) Autism. Lancet 383, 896–910.CrossRefGoogle ScholarPubMed
Larson, T, Anckarsäter, H, Gillberg, C, Ståhlberg, O, Carlström, E, Kadesjö, B, Råstam, M, Lichtenstein, P and Gillberg, C (2010) The autism-tics, AD/HD and other comorbidities inventory (A-TAC): further validation of a telephone interview for epidemiological research. BMC Psychiatry 10, 1.CrossRefGoogle ScholarPubMed
Lee, BK, Magnusson, C, Gardner, RM, Blomström, Å, Newschaffer, CJ, Burstyn, I, Karlsson, H and Dalman, C (2015) Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain, Behavior, and Immunity 44, 100–105.CrossRefGoogle ScholarPubMed
Li, X, Chauhan, A, Sheikh, AM, Patil, S, Chauhan, V, Li, XM, Ji, L, Brown, T and Malik, M (2009) Elevated immune response in the brain of autistic patients. Journal of Neuroimmunology 207(1–2), 111–116.CrossRefGoogle ScholarPubMed
Libbey, JE, Sweeten, TL, McMahon, WM and Fujinami, RS (2005) Autistic disorder and viral infections. Journal of NeuroVirology 11(1), 1–10.CrossRefGoogle ScholarPubMed
Bralten, J, Van Hulzen, KJ, Martens, MB, Galesloot, TE, Arias Vasquez, A, Kiemeney, LA, Buitelaar, JK, Muntjewerff, JW, Franke, B and Poelmans, G (2012) Autism spectrum disorders and autisticlike traits: similar etiology in the extreme end and the normal variation. Archives of General Psychiatry 69(1), 46–52.Google Scholar
Malik, M, Tauqeer, Z, Sheikh, AM, Wen, G, Nagori, A, Yang, K, Brown, WT and Li, X (2011) NF-κB signaling in the brain of autistic subjects. Mediators of Inflammation, 2011, Article ID 785265, 10. doi: 10.1155/2011/785265.CrossRefGoogle ScholarPubMed
Mårland, C, Lichtenstein, P, Degl’Innocenti, A, Larson, T, Råstam, M, Anckarsäter, H, Gillberg, C, Nilsson, T and Lundström, S (2017) The Autism-Tics, ADHD and other Comorbidities inventory (A-TAC): previous and predictive validity. BMC Psychiatry 17(1), 1–8.CrossRefGoogle ScholarPubMed
Masi, A, Breen, EJ, Alvares, GA, Glozier, N, Hickie, IB, Hunt, A, Hui, J, Beilby, J, Ravine, D, Wray, J, Whitehouse, AJO and Guastella, AJ (2017) Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder. Molecular Autism 8(1), 1–11.CrossRefGoogle ScholarPubMed
Meltzer, A and Van De Water, J (2017) The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 42(1), 284–298.CrossRefGoogle ScholarPubMed
Methot, L, Hermann, R, Tang, Y, Lo, R, Al-Jehani, H, Jhas, S, Svoboda, D, Slack, RS, Barker, PA and Stifani, S (2013) Interaction and antagonistic roles of NF-κB and Hes6 in the regulation of cortical neurogenesis. Molecular and Cellular Biology 33(14), 2797–2808.CrossRefGoogle ScholarPubMed
Naik, US, Gangadharan, C, Abbagani, K, Nagalla, B, Dasari, N and Manna, SK (2011) A study of nuclear transcription factor-kappa B in childhood autism. PLoS One 6(5), 1–6.CrossRefGoogle ScholarPubMed
Nardone, S and Elliott, E (2016) The interaction between the immune system and epigenetics in the etiology of autism spectrum disorders. Frontiers in Neuroscience 10(July), 1–9.CrossRefGoogle ScholarPubMed
Nudel, R, Simpson, NH, Baird, G, O’Hare, A, Conti-Ramsden, G, Bolton, PF, Hennessy, ER, Monaco, AP, Knight, JC, Winney, B, Fisher, SE, Newbury, DF, Slonims, V, Clark, A, Watson, J, Simonoff, E, Pickles, A, Everitt, A, Seckl, J, Cowie, H, Cohen, W, Nasir, J, Bishop, DVM and Simkin, Z (2014) Associations of HLA alleles with specific language impairment. Journal of Neurodevelopmental Disorders 6(1), 1–9.CrossRefGoogle ScholarPubMed
Nudel, R, Simpson, NH, Baird, G, O’Hare, A, Conti-Ramsden, G, Bolton, PF, Hennessy, ER, Monaco, AP, Knight, JC, Winney, B, Fisher, SE, Newbury, DF, Slonims, V, Clark, A, Watson, J, Simonoff, E, Pickles, A, Everitt, A, Seckl, J, Cowie, H, Cohen, W, Nasir, J, Bishop, DVM and Simkin, Z (2008) Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to the development of chronic Chagas’ cardiomyopathy among Trypanosoma cruzi-infected individuals. Molecular Immunology 45(1), 283–288.Google Scholar
Robinson, E, Koenen, KC, Mccormick, MC, Munir, K, Hallett, V, Happé, F, Ronald, A, Plomin, R and Ronald, A (2011) Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5% and 1%). Archives of General Psychiatry 68(11), 1113–1121.CrossRefGoogle Scholar
Robinson, EB, Lichtenstein, P, Anckarsater, H, Happe, F and Ronald, A (2013) Examining and interpreting the female protective effect against autistic behavior. Proceedings of the National Academy of Sciences of the United States of America 110(13), 5258–5262.CrossRefGoogle ScholarPubMed
Ronald, A, Butcher, LM, Docherty, S, Davis, OSP, Schalkwyk, LC, Craig, IW and Plomin, R (2010) A genome-wide association study of social and non-social autistic-like traits in the general population using pooled DNA, 500 K SNP microarrays and both community and diagnosed autism replication samples. Behavior Genetics 40(1), 31–45.CrossRefGoogle ScholarPubMed
Rossignol, D, Genuis, S and Frye, R (2014) Environmental toxicants and autism spectrum disorders: a systematic review. Translational Psychiatry 4, e360. doi: 10.1038/tp.2014.4 CrossRefGoogle ScholarPubMed
Schieve, LA, Tian, LH, Baio, J, Rankin, K, Rosenberg, D, Wiggins, L, Maenner, MJ, Yeargin-Allsopp, M, Durkin, M, Rice, C, King, L, Kirby, RS, Wingate, MS and Devine, O (2014) Population attributable fractions for three perinatal risk factors for autism spectrum disorders, 2002 and 2008 autism and developmental disabilities monitoring network. Annals of Epidemiology 24(4), 260–266.CrossRefGoogle ScholarPubMed
Shadrina, M, Bondarenko, EA and Slominsky, PA (2018) Genetics factors in major depression disease. Frontiers in Psychiatry 9(July), 1–18.CrossRefGoogle ScholarPubMed
Sheikh, AM, Malik, M, Wen, G, Chauhan, A, Chauhan, V, Gong, CX, Liu, F, Brown, WT and Li, X (2010) BDNF-Akt-Bcl2 antiapoptotic signaling pathway is compromised in the brain of autistic subjects. Journal of Neuroscience Research 88(12), 2641–2647.Google ScholarPubMed
Snow, WM, Stoesz, BM, Kelly, DM and Albensi, BC (2014) Roles for NF-κB and gene targets of NF-κB in synaptic plasticity, memory, and navigation. Molecular Neurobiology 49(2), 757–770.CrossRefGoogle ScholarPubMed
Stubbs, EG and Magenis, RE (1980) HLA and autism. Journal of Autism and Developmental Disorders 10(1), 15–19.CrossRefGoogle ScholarPubMed
Suchankova, P, Baghaei, F, Rosmond, R, Holm, G, Anckarsäter, H and Ekman, A (2011) Genetic variability within the S100B gene influences the personality trait self-directedness. Psychoneuroendocrinology 36(6), 919–923.CrossRefGoogle ScholarPubMed
Suchankova, P, Henningsson, S, Baghaei, F, Rosmond, R, Holm, G and Ekman, A (2009) Genetic variability within the innate immune system influences personality traits in women. Genes, Brain and Behavior 8(2), 212–217.CrossRefGoogle ScholarPubMed
Suchankova, P, Klang, J, Cavanna, C, Holm, G, Nilsson, S, Jönsson, EG and Ekman, A (2012) Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism? Journal of Psychiatry & Neuroscience 37(2), 122–128.CrossRefGoogle ScholarPubMed
Suchankova, P, Pettersson, R, Nordenström, K, Holm, G and Ekman, A (2012) Personality traits and the R668Q polymorphism located in the MMP-9 gene. Behavioural Brain Research 228(1), 232–235.CrossRefGoogle ScholarPubMed
Sullivan, PF and Geschwind, DH (2019) Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders. Cell 177, 162–183.CrossRefGoogle ScholarPubMed
Sweeten, TL, Bowyer, SL, Posey, DJ, Halberstadt, GM and McDougle, CJ (2003) Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics 112(5), e420–e420.CrossRefGoogle ScholarPubMed
The Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Molecular Autism 8(21), 1–17.Google Scholar
Tick, B, Bolton, P, Happé, F, Rutter, M and Rijsdijk, F (2016) Heritability of autism spectrum disorders: a meta-analysis of twin studies. The Journal of Child Psychology and Psychiatry and Allied Disciplines 57(5), 585–595.CrossRefGoogle ScholarPubMed
Torres, AR, Sweeten, TL, Johnson, RC, Odell, D, Westover, JB, Bray-Ward, P, Ward, DC, Davies, CJ, Thomas, AJ, Croen, LA and Benson, M (2016) Common genetic variants found in HLA and KIR immune genes in autism spectrum disorder. Frontiers in Neuroscience 10(OCT), 1–13.CrossRefGoogle ScholarPubMed
Torres, AR, Westover, JB and Rosenspire, AJ (2012) HLA immune function genes in autism. Autism Research and Treatment 2012, 1–13.CrossRefGoogle ScholarPubMed
Voineagu, I, Wang, X, Johnston, P, Lowe, JK, Tian, Y, Mill, J, Cantor, R, Blencowe, BJ, Daniel, H, Horvath, S, Mill, J, Cantor, R, Blencowe, BJ and Geschwind, DH (2013) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474(7351), 380–384.CrossRefGoogle Scholar
Wang, SS, Purdue, MP, Cerhan, JR, Zheng, T, Menashe, I, Armstrong, BK, Lan, Q, Hartge, P, Kricker, A, Zhang, Y, Morton, LM, Vajdic, CM, Holford, TR, Severson, RK, Grulich, A, Leaderer, BP, Davis, S, Cozen, W, Yeager, M, Chanock, SJ, Chatterjee, N and Rothman, N (2009) Common gene variants in the Tumor Necrosis Factor (TNF) and TNF receptor superfamilies and NF-kB transcription factors and non-hodgkin lymphoma risk. PLoS One 4(4), e5360. doi: 10.1371/journal.pone.0005360 CrossRefGoogle ScholarPubMed
Werling, DM (2016) The role of sex-differential biology in risk for autism spectrum disorder. Biology of Sex Differences 7(1), 1–18.CrossRefGoogle ScholarPubMed
Woodbury-Smith, M and Scherer, SW (2018) Progress in the genetics of autism spectrum disorder. Developmental Medicine & Child Neurology 60(5), 445–451.CrossRefGoogle ScholarPubMed
Young, AMH, Campbell, E, Lynch, S, Suckling, J and Powis, SJ (2011) Aberrant NF-kappaB expression in autism spectrum condition: a mechanism for neuroinflammation. Frontiers in Psychiatry 2(MAY), 1–8.CrossRefGoogle ScholarPubMed
Zeggini, E and Ioannidis, JPA (2009) Meta-analysis in genome-wide association studies. Pharmacogenomics 10(2), 191–201.CrossRefGoogle ScholarPubMed