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Percorrer por autor "Bailey, A.J."

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  • Convergence of genes and cellular pathways dysregulated in autism spectrum disorders
    Publication . Pinto, D.; Delaby, E.; Merico, D.; Barbosa, M.; Merikangas, A.; Klei, L; Thiruvahindrapuram, B.; Xu, X.; Ziman, R.; Wang, Z.; Vorstman, J.A.; Thompson, A.; Regan, R.; Pilorge, M.; Pellecchia, G.; Pagnamenta, A.T.; Oliveira, B.; Marshall, C.R.; Magalhães, T.R.; Lowe, J.K.; Howe, J.L.; Griswold, A.J.; Gilbert, J.; Duketis, E.; Dombroski, B.A.; De Jonge, M.V.; Cuccaro, M.; Crawford, E.L.; Correia, C.T.; Conroy, J.; Conceição, I.C; Chiocchetti, A.G.; Casey, J.P.; Cai, G.; Cabrol, C.; Bolshakova, N.; Bacchelli, E.; Anney, R.; Gallinger, S.; Cotterchio, M.; Casey, G.; Zwaigenbaum, L.; Wittemeyer, K.; Wing, K.; Wallace, S.; van Engeland, H.; Tryfon, A.; Thomson, S.; Soorya, L.; Rogé, B.; Roberts, W.; Poustka, F.; Mouga, S.; Minshew, N.; McInnes, L.A.; McGrew, S.G.; Lord, C.; Leboyer, M.; Le Couteur, A.S.; Kolevzon, A.; Jiménez González, P.; Jacob, S.; Holt, R.; Guter, S.; Green, J.; Green, A.; Gillberg, C.; Fernandez, B.A.; Duque, F.; Delorme, R.; Dawson, G.; Chaste, P.; Café, C.; Brennan, S.; Bourgeron, T.; Bolton, P.F.; Bölte, S.; Bernier, R.; Baird, G.; Bailey, A.J.; Anagnostou, E.; Almeida, J.; Wijsman, E.M.; Vieland, V.J.; Vicente, A.M.; Schellenberg, G.D.; Pericak-Vance, M.; Paterson, A.D.; Parr, J.R.; Oliveira, G.; Nurnberger, J.I.; Monaco, A.P.; Maestrini, E.; Klauck, S.M.; Hakonarson, H.; Haines, J.L.; Geschwind, D.H.; Freitag, C.M.; Folstein, S.E.; Ennis, S.; Coon, H.; Battaglia, A.; Szatmari, P.; Sutcliffe, J.S.; Hallmayer, J.; Gill, M.; Cook, E.H.; Buxbaum, J.D.; Devlin, B.; Gallagher, L.; Betancur, C.
    Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
    2014-05Artigo científico Acesso restrito Ver mais
  • Functional impact of global rare copy number variation in autism spectrum disorders
    Publication . Pinto, D.; Pagnamenta, A.T.; Klei, L.; Anney, R.; Merico, D.; Regan, R.; Conroy, J.; Magalhaes, T.R.; Correia, C.; Abrahams, B.S.; Almeida, J.; Bacchelli, E.; Bader, G.D.; Bailey, A.J.; Baird, G.; Battaglia, A.; Berney, T.; Bolshakova, N.; Bölte, S.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Brian, J.; Bryson, S.E.; Carson, A.R.; Casallo, G.; Casey, J.; Chung, B.H.; Cochrane, L.; Corsello, C.; Crawford, E.L.; Crossett, A.; Cytrynbaum, C.; Dawson, G.; de Jonge, M.; Delorme, R.; Drmic, I.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Fombonne, E.; Freitag, C.M.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Goldberg, J.; Green, A.; Green, J.; Guter, S.J.; Hakonarson, H.; Heron, E.A.; Hill, M.; Holt, R.; Howe, J.L.; Hughes, G.; Hus, V.; Igliozzi, R.; Kim, C.; Klauck, S.M.; Kolevzon, A.; Korvatska, O.; Kustanovich, V.; Lajonchere, C.M.; Lamb, J.A.; Laskawiec, M.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Lionel, A.C.; Liu, X.Q.; Lord, C.; Lotspeich, L.; Lund, S.C.; Maestrini, E.; Mahoney, W.; Mantoulan, C.; Marshall, C.R.; McConachie, H.; McDougle, C.J.; McGrath, J.; McMahon, W.M.; Merikangas, A.; Migita, O.; Minshew, N.J.; Mirza, G.K.; Munson, J.; Nelson, S.F.; Noakes, C.; Noor, A.; Nygren, G.; Oliveira, G.; Papanikolaou, K.; Parr, J.R.; Parrini, B.; Paton, T.; Pickles, A.; Pilorge, M.; Piven, J.; Ponting, C.P.; Posey, D.J.; Poustka, A.; Poustka, F.; Prasad, A.; Ragoussis, J.; Renshaw, K.; Rickaby, J.; Roberts, W.; Roeder, K.; Roge, B.; Rutter, M.L.; Bierut, L.J.; Rice, J.P.; Salt, J.; Sansom, K.; Sato, D.; Segurado, R.; Sequeira, A.F.; Senman, L.; Shah, N.; Sheffield, V.C.; Soorya, L.; Sousa, I.; Stein, O.; Sykes, N.; Stoppioni, V.; Strawbridge, C.; Tancredi, R.; Tansey, K.; Thiruvahindrapduram, B.; Thompson, A.P.; Thomson, S.; Tryfon, A.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Wallace, S.; Wang, K.; Wang, Z.; Wassink, T.H.; Webber, C.; Weksberg, R.; Wing, K.; Wittemeyer, K.; Wood, S.; Wu, J.; Yaspan, B.L.; Zurawiecki, D.; Zwaigenbaum, L.; Buxbaum, J.D.; Cantor, R.M.; Cook, E.H.; Coon, H.; Cuccaro, M.L.; Devlin, B.; Ennis, S.; Gallagher, L.; Geschwind, D.H.; Gill, M.; Haines, J.L.; Hallmayer, J.; Miller, J.; Monaco, A.P.; Nurnberger Jr, J.I.; Paterson, A.D.; Pericak-Vance, M.A.; Schellenberg, G.D.; Szatmari, P.; Vicente, A.M.; Vieland, V.J.; Wijsman, E.M.; Scherer, S.W.; Sutcliffe, J.S.; Betancur, C.
    The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
    2010-07-15Artigo científico Acesso aberto Ver mais
  • Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders
    Publication . Anney, R.J.; Kenny, E.M.; O'Dushlaine, C.; Parkhomenka, E.; Buxbaum, J.D.; Sutcliffe, J.; Gill, M.; Gallagher, L.; Bailey, A.J.; Fernandez, B.A.; Szatmari, P.; Nurnberger Jr, J.I.; McDougle, C.J.; Posey, D.J.; Lord, C.; Corsello, C.; Hus, V.; Buxbaum, J.D.; Kolevzon, A.; Soorya, L.; Parkhomenko, E.; Scherer, S.W.; Leventhal, B.L.; Dawson, G.; Vieland, V.J.; Hakonarson, H.; Glessner, J.T.; Kim, C.; Wang, K.; Schellenberg, G.D.; Devlin, B.; Klei, L.; Patterson, A.; Minshew, N.; Sutcliffe, J.S.; Haines, J.L.; Lund, S.C.; Thomson, S.; Yaspan, B.L.; Coon, H.; Miller, J.; McMahon, W.M.; Munson, J.; Marshall, C.R.; Estes, A.; Wijsman, EM.; The Autism Genome Project; Pinto, D.; Vincent, J.B.; Fombonne, E.; Betancur, C.; Delorme, R.; Leboyer, M.; Bourgeron, T.; Mantoulan, C.; Roge, B.; Tauber, M.; Freitag, C.M.; Poustka, F.; Duketis, E.; Klauck, S.M.; Poustka, A.; Papanikolaou, K.; Tsiantis, J.; Gallagher, L.; Gill, M.; Anney, R.; Bolshakova, N.; Brennan, S.; Hughes, G.; McGrath, J.; Merikangas, A.; Ennis, S.; Green, A.; Casey, J.P.; Conroy, J.M.; Regan, R.; Shah, N.; Maestrini, E.; Bacchelli, E.; Minopoli, F.; Stoppioni, V.; Battaglia, A.; Igliozzi, R.; Parrini, B.; Tancredi, R.; Oliveira, G.; Almeida, J.; Duque, F.; Vicente, A.M.; Correia, C.; Magalhaes, T.R.; Gillberg, C.; Nygren, G.; Jonge, M.D.; Van Engeland, H.; Vorstman, J.A.; Wittemeyer, K.; Baird, G.; Bolton, P.F; Rutter, M.L.; Green, J.; Lamb, J.A.; Pickles, A.; Parr, J.R.; Couteur, A.L.; Berney, T.; McConachie, H.; Wallace, S.; Coutanche, M.; Foley, S.; White, K.; Monaco, A.P.; Holt, R.; Farrar, P.; Pagnamenta, A.T.; Mirza, G.K.; Ragoussis, J.; Sousa, I.; Sykes, N.; Wing, K.; Hallmayer, J.; Cantor, R.M.; Nelson, S.F.; Geschwind, D.H.; Abrahams, B.S.; Volkmar, F.; Pericak-Vance, M.A.; Cuccaro, M.L.; Gilbert, J.; Cook, E.H.; Guter, S.J.; Jacob, S.
    Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.
    2011-04-27Artigo científico Acesso restrito Ver mais
  • A genome-wide scan for common alleles affecting risk for autism
    Publication . Anney, R.; Klei, L.; Pinto, D.; Regan, R.; Conroy, J.; Magalhaes, T.R.; Correia, C.; Abrahams, B.S.; Sykes, N.; Pagnamenta, A.T.; Almeida, J.; Bacchelli, E.; Bailey, A.J.; Baird, G.; Battaglia, A.; Berney, T.; Bolshakova, N.; Bölte, S.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Brian, J.; Carson, A.R.; Casallo, G.; Casey, J.; Chu, S.H.; Cochrane, L.; Corsello, C.; Crawford, E.L.; Crossett, A.; Dawson, G.; de Jonge, M.; Delorme, R.; Drmic, I.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Fombonne, E.; Freitag, C.M.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Goldberg, J.; Green, J.; Guter, S.J.; Hakonarson, H.; Heron, E.A.; Hill, M.; Holt, R.; Howe, J.L.; Hughes, G.; Hus, V.; Igliozzi, R.; Kim, C.; Klauck, S.M.; Kolevzon, A.; Korvatska, O.; Kustanovich, V.; Lajonchere, C.M.; Lamb, J.A.; Laskawiec, M.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Lionel, A.C.; Liu, X.Q.; Lord, C.; Lotspeich, L.; Lund, S.C.; Maestrini, E.; Mahoney, W.; Mantoulan, C.; Marshall, C.R.; McConachie, H.; McDougle, C.J.; McGrath, J.; McMahon, W.M.; Melhem, N.M.; Merikangas, A.; Migita, O.; Minshew, N.J.; Mirza, G.K.; Munson, J.; Nelson, S.F.; Noakes, C.; Noor, A.; Nygren, G.; Oliveira, G.; Papanikolaou, K.; Parr, J.R.; Parrini, B.; Paton, T.; Pickles, A.; Piven, J.; Posey, D.J.; Poustka, A.; Poustka, F.; Prasad, A.; Ragoussis, J.; Renshaw, K.; Rickaby, J.; Roberts, W.; Roeder, K.; Roge, B.; Rutter, M.L.; Bierut, L.J.; Rice, J.P.; Salt, J.; Sansom, K.; Sato, D.; Segurado, R.; Senman, L.; Shah, N.; Sheffield, V.C.; Soorya, L.; Sousa, I.; Stoppioni, V.; Strawbridge, C.; Tancredi, R.; Tansey, K.; Thiruvahindrapduram, B.; Thompson, A.P.; Thomson, S.; Tryfon, A.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Wallace, S.; Wang, K.; Wang, Z.; Wassink, T.H.; Wing, K.; Wittemeyer, K.; Wood, S.; Yaspan, B.L.; Zurawiecki, D.; Zwaigenbaum, L.; Betancur, C.; Buxbaum, J.D.; Cantor, R.M.; Cook, E.H.; Coon, H.; Cuccaro, M.L.; Gallagher, L.; Geschwind, D.H.; Gill, M.; Haines, J.L.; Miller, J.; Monaco, A.P.; Nurnberger Jr, J.I.; Paterson, A.D.; Pericak-Vance, M.A.; Schellenberg, G.D.; Scherer, S.W.; Sutcliffe, J.S.; Szatmari, P.; Vicente, A.M.; Vieland, V.J.; Wijsman, E.M.; Devlin, B.; Ennis, S.; Hallmayer, J.
    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
    2010-10-15Artigo científico Acesso aberto Ver mais
  • A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder
    Publication . Casey, J.P.; Magalhaes, T.; Conroy, J.M.; Regan, R.; Shah, N.; Anney, R.; Shields, D.C.; Abrahams, B.S.; Almeida, J.; Bacchelli, E.; Bailey, A.J.; Piven, J.; Posey, D.J.; Poustka, A.; Poustka, F.; Ragoussis, J.; Roge, B.; Rutter, M.L.; Sequeira, A.F.; Soorya, L.; Sousa, I.; Wittemeyer, K.; Sykes, N.; Stoppioni, V.; Tancredi, R.; Tauber, M.; Thompson, A.P.; Thomson, S.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Yaspan, B.L.; Vorstman, J.A.; Wallace, S.; Wang, K.; Wassink, T.H.; White, K.; Wing, K.; Zwaigenbaum, L.; Betancur, C.; Buxbaum, J.D.; Cantor, R.M.; Cook, E.H.; Coon, H.; Cuccaro, M.L.; Geschwind, D.H.; Baird, G.; Haines, J.L.; Hallmayer, J.; Monaco, A.P.; Nurnberger, J.I. Jr; Pericak-Vance, M.A.; Schellenberg, G.D.; Scherer, S.W.; Sutcliffe, J.S.; Szatmari, P.; Vieland, V.J.; Battaglia, A.; Wijsman, E.M.; Green, A.; Gill, M.; Gallagher, L.; Vicente, A.M.; Ennis, S.; Berney, T.; Bolshakova, N.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Cali, P.; Correia, C.; Corsello, C.; Coutanche, M.; Dawson, G.; de Jonge, M.; Delorme, R.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Foley, S.; Fombonne, E.; Freitag, C.M.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Green, J.; Guter, S.J.; Hakonarson, H.; Holt, R.; Hughes, G.; Hus, V.; Igliozzi, R.; Kim, C.; Klauck, S.M.; Kolevzon, A.; Lamb, J.A.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Lord, C.; Lund, S.C.; Maestrini, E.; Mantoulan, C.; Marshall, C.R.; McConachie, H.; McDougle, C.J.; McGrath, J.; McMahon, W.M.; Merikangas, A.; Miller, J.; Minopoli, F.; Mirza, G.K.; Munson, J.; Nelson, S.F.; Nygren, G.; Oliveira, G.; Pagnamenta, A.T.; Papanikolaou, K.; Parr, J.R.; Parrini, B.; Pickles, A.; Pinto, D.
    Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
    2011-10-14Artigo científico Acesso restrito Ver mais
  • The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism
    Publication . Hadley, D.; Wu, Z.L.; Kao, C.; Kini, A.; Mohamed-Hadley, A.; Thomas, K.; Vazquez, L.; Qiu, H.; Mentch, F.; Pellegrino, R.; Kim, C.; Connolly, J.; Glessner, J.; Hakonarson, H.; Pinto, D.; Merikangas, A.; Klei, L.; Vorstman, J.A.; Thompson, A.; Regan, R.; Pagnamenta, A.T.; Oliveira, B.; Magalhaes, T.R.; Gilbert, J.; Duketis, E.; De Jonge, M.V.; Cuccaro, M.; Correia, C.T.; Conroy, J.; Conceição, I.C.; Chiocchetti, A.G.; Casey, J.P.; Bolshakova, N.; Bacchelli, E.; Anney, R.; Zwaigenbaum, L.; Wittemeyer, K.; Wallace, S.; Engeland, Hv; Soorya, L.; Rogé, B.; Roberts, W.; Poustka, F.; Mouga, S.; Minshew, N.; McGrew, S.G.; Lord, C.; Leboyer, M.; Le Couteur, A.S.; Kolevzon, A.; Jacob, S.; Guter, S.; Green, J.; Green, A.; Gillberg, C.; Fernandez, B.A.; Duque, F.; Delorme, R.; Dawson, G.; Café, C.; Brennan, S.; Bourgeron, T.; Bolton, P.F.; Bölte, S.; Bernier, R.; Baird, G.; Bailey, A.J.; Anagnostou, E.; Almeida, J.; Wijsman, E.M.; Vieland, V.J.; Vicente, A.M.; Schellenberg, G.D.; Pericak-Vance, M.; Paterson, A.D.; Parr, J.R.; Oliveira, G.; Almeida, J.; Café, C.; Mouga, S.; Correia, C.; Nurnberger, J.I.; Monaco, A.P.; Maestrini, E.; Klauck, S.M.; Hakonarson, H.; Haines, J.L.; Geschwind, D.H.; Freitag, C.M.; Folstein, S.E.; Ennis, S.; Coon, H.; Battaglia, A.; Szatmari, P.; Sutcliffe, J.S.; Hallmayer, J.; Gill, M.; Cook, E.H.; Buxbaum, J.D.; Devlin, B.; Gallagher, L.; Betancur, C.; Scherer, S.W.
    Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions.
    2014-06-13Artigo científico Acesso aberto Ver mais