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1. Nature Farming and Microbial Applications

Author: Hiu-lian Xu, Hiroshi Umemura, James F. Parr Jr, Hiu-lian Xu, Hiroshi Umemura, and James F. Parr Jr
Subjects: Organic farming, Organic fertilizers, Microbial inoculants
Abstract: Produce more abundant, high-quality crops with the information you'll find in this book!Recent concerns over environmental pollution and food quality degradation caused by the excessive use of chemicals have prompted scientists and policymakers to re-evaluate modern agricultural processes and search for alternatives that will aid in the production of healthy foods and the protection of our environment. Nature Farming and Microbial Applications summarizes current research in the field, highlighting unique practices such as the use of microbial inoculants and various alternatives to chemical fertilizers and pesticides. The principles of nature farming, as set forth by Japanese philosopher Mokichi Okada, must fulfill these requirements: producing safe and nutritious food that promotes good health providing economic and spiritual benefits to both producers and consumers being sustainable and easily practiced conserving and protecting the environment producing sufficient high-quality food for an expanding world populationTo this end, Nature Farming and Microbial Applications addresses issues of concern to organic farmers, including: soil fertility pest control effective microorganisms photosynthesis transpiration plant-water relations stress resistance of growing cropsThis well-referenced volume contains unique and original methods of modeling and analysis. It will be used again and again as a reference source for students and researchers.
Published: 2024

2. Transfer of the marine red alga Erythrocystis saccata (Rhodomelaceae, Rhodophyta) to the tribe Streblocladieae inferred from organellar genome analysis

Author: AMOS, DEE, primary, AGUILAR, VILMA, additional, BARBER-SCOTT, KRISTIN, additional, BUSTAMANTE, DANILO E., additional, CALDERON, MARTHA S., additional, CARRASCO, ROMAN, additional, CARRION, JOIS V., additional, CASTRO, NANCY, additional, CELSO, DALYLAH, additional, CORTES CEDILLO, STEPHANIE M., additional, CORTES, RODRIGO, additional, DAO, LONG, additional, DE SANTOS, SONIA, additional, EBIE, ZACHARY, additional, EVANGELISTA, LUKE, additional, FERNANDEZ, SAMIA L., additional, FLORES, GABRIELA, additional, GARCIA, LINETT, additional, GONZALEZ, ERIC, additional, HERNANDEZ, ALEJANDRO, additional, HERNANDEZ, MARIO O., additional, HUGHEY, JEFFERY R., additional, LUNA, LUIS, additional, MARQUEZ, KARINA, additional, MARTINEZ, VANESSA, additional, MENDOZA, JANI E., additional, MIRASSOU, LAUREN, additional, MURILLO, CALI, additional, PARR JR., MICHAEL, additional, PEREZ, JHORDY, additional, PEREZ-SANTANA, ITZEL, additional, PEREZ, HORACIO, additional, QUEZADA, ALYNNA, additional, QUIZON, SEBASTIAN, additional, SANDBERG, SHAWN, additional, SANTOS, ARIANA, additional, TAPIA, JESSIE, additional, TINEO, DANIEL, additional, and VANG, MAI N., additional
Published: 2021
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3. How to buck preemption in drug cases.

Author: Parr, Jr., Edward J.
Subjects: Fraud -- Cases, Torts -- Cases, Exclusive and concurrent legislative powers -- Cases, Buckman Co. v. Plaintiffs' Legal Committee (121 S. Ct. 1012 (2001)), Company legal issue
Abstract: When the Supreme Court ruled that a state fraud-on-the-FDA claim was impliedly preempted by federal law in the medical device case Buckman Co. v. Plaintiffs' Legal Committee (1) in February, [...]
Published: 2001

4. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author: Haworth, S, Shapland, CY, Hayward, C, Prins, BP, Felix, JF, Medina-Gomez, C, Rivadeneira, F, Wang, C, Ahluwalia, TS, Vrijheid, M, Guxens, M, Sunyer, J, Tachmazidou, I, Walter, K, Iotchkova, V, Jackson, A, Cleal, L, Huffmann, J, Min, JL, Sass, L, Timmers, PRHJ, Al Turki, S, Anderson, CA, Anney, R, Antony, D, Artigas, MS, Ayub, M, Bala, S, Barrett, JC, Barroso, I, Beales, P, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, DA, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Danecek, P, Day, INM, Day-Williams, A, Dominiczak, A, Down, T, Du, Y, Dunham, I, Durbin, R, Edkins, S, Ekong, R, Ellis, P, Evans, DM, Farooqi, IS, Fitzpatrick, DR, Flicek, P, Floyd, J, Foley, AR, Franklin, CS, Futema, M, Gallagher, L, Gaunt, TR, Geihs, M, Geschwind, D, Greenwood, CMT, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, AE, Holmans, P, Howie, B, Huang, J, Huang, L, Hubbard, T, Humphries, SE, Hurles, ME, Hysi, P, Jackson, DK, Jamshidi, Y, Joyce, C, Karczewski, KJ, Kaye, J, Keane, T, Kemp, JP, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, van Kogelenberg, M, Kolb-Kokocinski, A, Lachance, G, Langford, C, Lawson, D, Lee, I, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M, MacArthur, DG, Mangino, M, Marchini, J, Marenne, G, Maslen, J, Mathieson, I, McCarthy, S, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Memari, Y, Metrustry, S, Migone, N, Mitchison, HM, Moayyeri, A, Morris, A, Morris, J, Muddyman, D, Muntoni, F, Northstone, K, O'Donovan, MC, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, MJ, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, JR, Paternoster, L, Paunio, T, Payne, F, Payne, SJ, Perry, JRB, Pietilainen, O, Plagnol, V, Pollitt, RC, Porteous, DJ, Povey, S, Quail, MA, Quaye, L, Raymond, FL, Rehnstrom, K, Richards, JB, Ridout, CK, Ring, S, Ritchie, GRS, Roberts, N, Robinson, RL, Savage, DB, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, RH, Semple, RK, Serra, E, Sharp, SI, Shaw, A, Shihab, HA, Shin, S-Y, Skuse, D, Small, KS, Smee, C, Smith, BH, Soranzo, N, Southam, L, Spasic-Boskovic, O, Spector, TD, St Clair, D, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Taylor, R, Tian, J, Tobin, MD, Valdes, AM, Vandersteen, AM, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whyte, T, Williams, HJ, Williamson, KA, Wilson, C, Wilson, SG, Wong, K, Xu, C, Yang, J, Zhang, F, Zhang, P, Zheng, H-F, Smith, GD, Fisher, SE, Wilson, JF, Cole, TJ, Fernandez-Orth, D, Bonnelykke, K, Bisgaard, H, Pennell, CE, Jaddoe, VWV, Dedoussis, G, Timpson, N, Zeggini, E, Vitart, V, St Pourcain, B, UK10K Consortium, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, and Child and Adolescent Psychiatry / Psychology
Abstract: Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.
Published: 2019

5. 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

Author: Anney, RJL, Ripke, S, Anttila, V, Grove, J, Holmans, P, Huang, H, Klei, L, Lee, PH, Medland, SE, Neale, B, Robinson, E, Weiss, LA, Zwaigenbaum, L, Yu, TW, Wittemeyer, K, Willsey, AJ, Wijsman, EM, Werge, T, Wassink, TH, Waltes, R, Walsh, CA, Wallace, S, Vorstman, JAS, Vieland, VJ, Vicente, AM, Vanengeland, H, Tsang, K, Thompson, AP, Szatmari, P, Svantesson, O, Steinberg, S, Stefansson, K, Stefansson, H, State, MW, Soorya, L, Silagadze, T, Scherer, SW, Schellenberg, GD, Sandin, S, Sanders, SJ, Saemundsen, E, Rouleau, GA, Rogé, B, Roeder, K, Roberts, W, Reichert, J, Reichenberg, A, Rehnström, K, Regan, R, Poustka, F, Poultney, CS, Piven, J, Pinto, D, Pericak-Vance, MA, Pejovic-Milovancevic, M, Pedersen, MG, Pedersen, CB, Paterson, AD, and Parr, JR
Subjects: mental disorders
Abstract: © 2017 The Author(s). Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR)
Published: 2017
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6. De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder

Author: Babbs, C, Lloyd, D, Pagnamenta, A, Twigg, SR, Green, J, McGowan, S, Mirza, G, Naples, R, Sharma, V, Volpi, E, Buckle, V, Wall, SA, Knight, S, Parr, JR, and Wilkie, A
Subjects: Psychiatry, Gene Rearrangement, Male, Chromosomes, Human, Pair 22, Infant, Sequence Analysis, DNA, Chromosome Breakpoints, Chromosomal, Child Development Disorders, Pervasive, mental disorders, Mutation, Genetics, Humans, Cognitive and Behavioural Genetics, Molecular genetics, Clinical genetics, Child, In Situ Hybridization, Fluorescence, Transcription Factors
Abstract: BACKGROUND: Autism spectrum disorders (ASDs) are common and have a strong genetic basis, yet the cause of ∼70-80% ASDs remains unknown. By clinical cytogenetic testing, we identified a family in which two brothers had ASD, mild intellectual disability and a chromosome 22 pericentric inversion, not detected in either parent, indicating de novo mutation with parental germinal mosaicism. We hypothesised that the rearrangement was causative of their ASD and localised the chromosome 22 breakpoints. METHODS: The rearrangement was characterised using fluorescence in situ hybridisation, Southern blotting, inverse PCR and dideoxy-sequencing. Open reading frames and intron/exon boundaries of the two physically disrupted genes identified, TCF20 and TNRC6B, were sequenced in 342 families (260 multiplex and 82 simplex) ascertained by the International Molecular Genetic Study of Autism Consortium (IMGSAC). RESULTS: IMGSAC family screening identified a de novo missense mutation of TCF20 in a single case and significant association of a different missense mutation of TCF20 with ASD in three further families. Through exome sequencing in another project, we independently identified a de novo frameshifting mutation of TCF20 in a woman with ASD and moderate intellectual disability. We did not identify a significant association of TNRC6B mutations with ASD. CONCLUSIONS: TCF20 encodes a transcriptional coregulator (also termed SPBP) that is structurally and functionally related to RAI1, the critical dosage-sensitive protein implicated in the behavioural phenotypes of the Smith-Magenis and Potocki-Lupski 17p11.2 deletion/duplication syndromes, in which ASD is frequently diagnosed. This study provides the first evidence that mutations in TCF20 are also associated with ASD.
Published: 2014

7. A longitudinal, observational study examining the relationships of patient satisfaction with services and mental well-being to their clinical course in young people with Type 1 diabetes mellitus during transition from child to adult health services

Author: Gray, S, Cheetham, T, McConachie, H, Mann, KD, Parr, JR, Pearce, MS, Colver, A, Bate, A, Bennett, C, Dovey-Pearce, G, McDonagh, J, Rapley, T, Reape, D, Vale, L, Chater, N, Gleeson, H, Bem, A, Bennett, S, Billson, A, Bruce, S, Howlett, D, Huma, Z, Linden, M, Lohan, M, Meek, M, Milne, J, Owens, Julie-Anne, Thalange, N, Gray, S, Cheetham, T, McConachie, H, Mann, KD, Parr, JR, Pearce, MS, Colver, A, Bate, A, Bennett, C, Dovey-Pearce, G, McDonagh, J, Rapley, T, Reape, D, Vale, L, Chater, N, Gleeson, H, Bem, A, Bennett, S, Billson, A, Bruce, S, Howlett, D, Huma, Z, Linden, M, Lohan, M, Meek, M, Milne, J, Owens, Julie-Anne, and Thalange, N
Published: 2018

8. How well do services for young people with long term conditions deliver features proposed to improve transition?

Author: Colver, A, Pearse, R, Watson, RM, Fay, M, Rapley, T, Mann, KD, Le Couteur, A, Parr, JR, McConachie, H, Transition Collaborative Group, Bennett, C, Dovey-Pearce, G, Maniatopoulos, G, McDonagh, J, Reape, D, Vale, L, Chater, N, Gleeson, H, Bem, A, Bennett, S, Billson, A, Bruce, S, Cheetham, T, Howlett, D, Huma, Z, Linden, M, Lohan, M, Meek, M, Milne, J, Owens, Julie-Anne, Regan, F, Thalange., N, Colver, A, Pearse, R, Watson, RM, Fay, M, Rapley, T, Mann, KD, Le Couteur, A, Parr, JR, McConachie, H, Transition Collaborative Group, Bennett, C, Dovey-Pearce, G, Maniatopoulos, G, McDonagh, J, Reape, D, Vale, L, Chater, N, Gleeson, H, Bem, A, Bennett, S, Billson, A, Bruce, S, Cheetham, T, Howlett, D, Huma, Z, Linden, M, Lohan, M, Meek, M, Milne, J, Owens, Julie-Anne, Regan, F, and Thalange., N
Abstract: BACKGROUND: For young people with long-term conditions, transition from child to adult-oriented health services is a critical period which, if not managed well, may lead to poor outcomes. There are features of transition services which guidance and research suggest improve outcomes. We studied nine such features, calling them 'proposed beneficial features': age-banded clinic; meet adult team before transfer; promotion of health self-efficacy; written transition plan; appropriate parent involvement; key worker; coordinated team; holistic life-skills training; transition manager for clinical team. We aimed to describe the extent to which service providers offer these nine features, and to compare this with young people's reported experience of them. METHODS: A longitudinal, mixed methods study followed 374 young people as their care moved from child to adult health services. Participants had type 1 diabetes, cerebral palsy or autism spectrum disorder with additional mental health difficulties. Data are reported from the first two visits, one year apart. RESULTS: Three hundred four (81.3%) of the young people took part in the second visit (128 with diabetes, 91 with autism, 85 with cerebral palsy). Overall, the nine proposed beneficial features of transition services were poorly provided. Fewer than half of services stated they provided an age-banded clinic, written transition plan, transition manager for clinical team, a protocol for promotion of health self-efficacy, or holistic life-skills training. To varying degrees, young people reported that they had not experienced the features which services said they provided. For instance, the agreement for written transition plan, holistic life-skills training and key worker, was 30, 43 and 49% respectively. Agreement was better for appropriate parent involvement, age-banded clinic, promotion of health self-efficacy and coordinated team at 77, 77, 80 and 69% respectively. Variation in the meaning of the features as experien
Published: 2018

9. A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions

Author: Colver, A, McConachie, H, Le Couteur, A, Dovey-Pearce, G, Mann, KD, McDonagh, JE, Pearce, MS, Vale, L, Merrick, H, Parr, JR, Transition Collaborative Group, Owens, Julie-Anne, Colver, A, McConachie, H, Le Couteur, A, Dovey-Pearce, G, Mann, KD, McDonagh, JE, Pearce, MS, Vale, L, Merrick, H, Parr, JR, Transition Collaborative Group, and Owens, Julie-Anne
Abstract: BACKGROUND: Most evidence about what works in transitional care comes from small studies in single clinical specialties. We tested the hypothesis that exposures to nine recommended features of transitional healthcare were associated with better outcomes for young people with long-term conditions during transition from child-centred to adult-oriented health services. METHODS: This is a longitudinal, observational cohort study in UK secondary care including 374 young people, aged 14-18.9 years at recruitment, with type 1 diabetes (n = 150), cerebral palsy (n = 106) or autism spectrum disorder with an associated mental health problem (n = 118). All were pre-transfer and without significant learning disability. We approached all young people attending five paediatric diabetes centres, all young people with autism spectrum disorder attending four mental health centres, and randomly selected young people from two population-based cerebral palsy registers. Participants received four home research visits, 1 year apart and 274 participants (73%) completed follow-up. Outcome measures were Warwick Edinburgh Mental Wellbeing Scale, Mind the Gap Scale (satisfaction with services), Rotterdam Transition Profile (Participation) and Autonomy in Appointments. RESULTS: Exposure to recommended features was 61% for 'coordinated team', 53% for 'age-banded clinic', 48% for 'holistic life-skills training', 42% for 'promotion of health self-efficacy', 40% for 'meeting the adult team before transfer', 34% for 'appropriate parent involvement' and less than 30% for 'written transition plan', 'key worker' and 'transition manager for clinical team'. Three features were strongly associated with improved outcomes. (1) 'Appropriate parent involvement', example association with Wellbeing (b = 4.5, 95% CI 2.0-7.0, p = 0.001); (2) 'Promotion of health self-efficacy', example association with Satisfaction with Services (b = - 0.5, 95% CI - 0.
Published: 2018

10. The Hospital Anxiety and Depression scale: Factor structure and psychometric properties in older adolescents and young adults with autism spectrum disorder

Author: Uljarevic, M, Richdale, AL, McConachie, H, Hedley, D, Cai, RY, Merrick, H, Parr, JR, Le Couteur, A, Uljarevic, M, Richdale, AL, McConachie, H, Hedley, D, Cai, RY, Merrick, H, Parr, JR, and Le Couteur, A
Published: 2018

11. Parents Suggest Which Indicators of Progress and Outcomes Should be Measured in Young Children with Autism Spectrum Disorder

Author: McConachie, H, Livingstone, N, Morris, C, Beresford, B, Le Couteur, A, Gringras, P, Garland, D, Jones, G, Macdonald, G, Williams, K, Parr, JR, McConachie, H, Livingstone, N, Morris, C, Beresford, B, Le Couteur, A, Gringras, P, Garland, D, Jones, G, Macdonald, G, Williams, K, and Parr, JR
Abstract: Evaluation of interventions for children with autism spectrum disorder (ASD) is hampered by the multitude of outcomes measured and tools used. Measurement in research with young children tends to focus on core impairments in ASD. We conducted a systematic review of qualitative studies of what matters to parents. Parent advisory groups completed structured activities to explore their perceptions of the relative importance of a wide range of outcome constructs. Their highest ranked outcomes impacted directly on everyday life and functioning (anxiety, distress, hypersensitivity, sleep problems, happiness, relationships with brothers and sisters, and parent stress). Collaboration between professionals, researchers and parents/carers is required to determine an agreed core set of outcomes to use across evaluation research.
Published: 2018

12. Autism: in search of susceptibility genes

Author: Lamb, JA, Parr, JR, Bailey, AJ, and Monaco, AP
Subjects: mental disorders
Abstract: Autism is a neurodevelopmental disorder of unknown etiology. There is convincing data for the involvement of genetic factors in the development of autism, and the absence of any consistent evidence for an environmental, neuroanatomical, or biochemical cause has led to an increasing number of genetic studies to determine the basis of this complex disorder. The results of recent genetic linkage and candidate gene studies are reviewed in relation to the challenge of clinical and genetic heterogeneity, and prospects for the future of genetic research in autism are considered.
Published: 2016
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13. Deep brain stimulation: an effective treatment for idiopathic dystonia

Author: Parr, JR, Andrew, M, Joint, C, Green, A, Gregory, R, Scott, R, Aziz, T, and Mcshane, M
Published: 2016

14. Economical iontophoresis for dentistry.

Author: Parr, Jr., Olan D. and Brokaw, William C.
Subjects: IONTOPHORESIS, DENTISTRY, IONS, DENTAL equipment, DENTAL caries, DENTAL pulp cavities, ELECTROTHERAPEUTICS, PROSTHODONTICS, ELECTRONIC probes
Abstract: The article offers information on the technique of iontophoresis in dentistry and the components and use of an iontophoretic unit. Iontophoresis is known to be a process in which a low-voltage current is used to increase the rate of penetration of ions for therapeutic reasons. This therapy has played a major role in dentistry in the treatment of oral cavities, dentinal hypersensitivity and sterilization of root canal. The iontophoretic unit consists of several elements including test probes with banana plugs, jumbo paper clips and battery snap. The portable and economical unit, which has undergone improvements over the years, is believed to be safe and its results are immediate and long lasting.
Published: 1989

15. Simple fabrication of text and diagram slides for dental presentations.

Author: Lindsay, Byron W. and Parr, Jr., Olan D.
Subjects: FILMSTRIPS, LECTURES & lecturing, DENTISTRY, CHARTS, diagrams, etc., DENTAL care, MEDICAL sciences, RESEARCH
Abstract: The article presents a research which explains several techniques of making quality text slides with minimal cost, equipment and efforts for the presentation of dental lectures. Under the research Kodak Vericolor (SO-279) slide film from Eastman Kodak Co. and Roscolux theatrical gels from Rosco Inc. as filters were used. The research concludes that, image of any presenter is enhanced by a professional-quality text slides, and use of the earlier mentioned equipments as filters, is a simple and inexpensive way of producing good quality text and diagram slides.
Published: 1987

16. G95 The Drooling Reduction Intervention (DRI) trial: Is hyoscine or glycopyrronium more effective and acceptable for the treatment of drooling in children with neurodisability?

Author: Parr, JR, primary, Todhunter, E, additional, Pennington, L, additional, Cole, M, additional, Morrison, J, additional, Stocken, D, additional, and Colver, A, additional
Published: 2016
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17. G29 Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment

Author: Andrew, MJ, primary, Parr, JR, additional, Montague-Johnson, C, additional, Baker, BL, additional, Holmes, J, additional, Laler, K, additional, Atkinson, J, additional, Braddick, OJ, additional, and Sullivan, PB, additional
Published: 2016
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18. The UK10K project identifies rare variants in health and disease

Author: Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Soranzo, N, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, S-Y, Small, KS, Artigas, MS, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, H-F, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lonnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnstrom, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, GL, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, Maerz, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, van Duijn, CM, van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G, Zhang, W, Walter, K, Min, JL, Huang, J, Crooks, L, Memari, Y, McCarthy, S, Perry, JRB, Xu, C, Futema, M, Lawson, D, Iotchkova, V, Schiffels, S, Hendricks, AE, Danecek, P, Li, R, Floyd, J, Wain, LV, Barroso, I, Humphries, SE, Hurles, ME, Zeggini, E, Barrett, JC, Plagnol, V, Richards, JB, Greenwood, CMT, Timpson, NJ, Durbin, R, Soranzo, N, Bala, S, Clapham, P, Coates, G, Cox, T, Daly, A, Du, Y, Edkins, S, Ellis, P, Flicek, P, Guo, X, Huang, L, Jackson, DK, Joyce, C, Keane, T, Kolb-Kokocinski, A, Langford, C, Li, Y, Liang, J, Lin, H, Liu, R, Maslen, J, Muddyman, D, Quail, MA, Stalker, J, Sun, J, Tian, J, Wang, G, Wang, J, Wang, Y, Wong, K, Zhang, P, Birney, E, Boustred, C, Chen, L, Clement, G, Cocca, M, Smith, GD, Day, INM, Day-Williams, A, Down, T, Dunham, I, Evans, DM, Gaunt, TR, Geihs, M, Hart, D, Howie, B, Hubbard, T, Hysi, P, Jamshidi, Y, Karczewski, KJ, Kemp, JP, Lachance, G, Lek, M, Lopes, M, MacArthur, DG, Marchini, J, Mangino, M, Mathieson, I, Metrustry, S, Moayyeri, A, Northstone, K, Panoutsopoulou, K, Paternoster, L, Quaye, L, Ring, S, Ritchie, GRS, Shihab, HA, Shin, S-Y, Small, KS, Artigas, MS, Southam, L, Spector, TD, St Pourcain, B, Surdulescu, G, Tachmazidou, I, Tobin, MD, Valdes, AM, Visscher, PM, Ward, K, Wilson, SG, Yang, J, Zhang, F, Zheng, H-F, Anney, R, Ayub, M, Blackwood, D, Bolton, PF, Breen, G, Collier, DA, Craddock, N, Curran, S, Curtis, D, Gallagher, L, Geschwind, D, Gurling, H, Holmans, P, Lee, I, Lonnqvist, J, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Morris, J, O'Donovan, MC, Owen, MJ, Palotie, A, Parr, JR, Paunio, T, Pietilainen, O, Rehnstrom, K, Sharp, SI, Skuse, D, St Clair, D, Suvisaari, J, Walters, JTR, Williams, HJ, Bochukova, E, Bounds, R, Dominiczak, A, Farooqi, IS, Keogh, J, Marenne, GL, Morris, A, O'Rahilly, S, Porteous, DJ, Smith, BH, Wheeler, E, Al Turki, S, Anderson, CA, Antony, D, Beales, P, Bentham, J, Bhattacharya, S, Calissano, M, Carss, K, Chatterjee, K, Cirak, S, Cosgrove, C, Fitzpatrick, DR, Foley, AR, Franklin, CS, Grozeva, D, Mitchison, HM, Muntoni, F, Onoufriadis, A, Parker, V, Payne, F, Raymond, FL, Roberts, N, Savage, DB, Scambler, P, Schmidts, M, Schoenmakers, N, Semple, RK, Serra, E, Spasic-Boskovic, O, Stevens, E, van Kogelenberg, M, Vijayarangakannan, P, Williamson, KA, Wilson, C, Whyte, T, Ciampi, A, Oualkacha, K, Bobrow, M, Griffin, H, Kaye, J, Kennedy, K, Kent, A, Smee, C, Charlton, R, Ekong, R, Khawaja, F, Lopes, LR, Migone, N, Payne, SJ, Pollitt, RC, Povey, S, Ridout, CK, Robinson, RL, Scott, RH, Shaw, A, Syrris, P, Taylor, R, Vandersteen, AM, Amuzu, A, Casas, JP, Chambers, JC, Dedoussis, G, Gambaro, G, Gasparini, P, Isaacs, A, Johnson, J, Kleber, ME, Kooner, JS, Langenberg, C, Luan, J, Malerba, G, Maerz, W, Matchan, A, Morris, R, Nordestgaard, BG, Benn, M, Scott, RA, Toniolo, D, Traglia, M, Tybjaerg-Hansen, A, van Duijn, CM, van Leeuwen, EM, Varbo, A, Whincup, P, Zaza, G, and Zhang, W
Abstract: The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.
Published: 2015

19. Deep brain stimulation: an effective treatment for idiopathic dystonia

Author: Parr, JR, Andrew, M, Joint, C, Green, A, Gregory, R, Scott, R, Aziz, T, and Mcshane, MA
Published: 2006

20. Synaptic, transcriptional and chromatin genes disrupted in autism.

Author: De Rubeis, S, He, X, Goldberg, AP, Poultney, CS, Samocha, K, Cicek, AE, Kou, Y, Liu, L, Fromer, M, Walker, S, Singh, T, Klei, L, Kosmicki, J, Shih-Chen, F, Aleksic, B, Biscaldi, M, Bolton, PF, Brownfeld, JM, Cai, J, Campbell, NG, Carracedo, A, Chahrour, MH, Chiocchetti, AG, Coon, H, Crawford, EL, Curran, SR, Dawson, G, Duketis, E, Fernandez, BA, Gallagher, L, Geller, E, Guter, SJ, Hill, RS, Ionita-Laza, J, Jimenz Gonzalez, P, Kilpinen, H, Klauck, SM, Kolevzon, A, Lee, I, Lei, I, Lei, J, Lehtimäki, T, Lin, C-F, Ma'ayan, A, Marshall, CR, McInnes, AL, Neale, B, Owen, MJ, Ozaki, N, Parellada, M, Parr, JR, Purcell, S, Puura, K, Rajagopalan, D, Rehnström, K, Reichenberg, A, Sabo, A, Sachse, M, Sanders, SJ, Schafer, C, Schulte-Rüther, M, Skuse, D, Stevens, C, Szatmari, P, Tammimies, K, Valladares, O, Voran, A, Li-San, W, Weiss, LA, Willsey, AJ, Yu, TW, Yuen, RKC, DDD Study, Homozygosity Mapping Collaborative for Autism, UK10K Consortium, Cook, EH, Freitag, CM, Gill, M, Hultman, CM, Lehner, T, Palotie, A, Schellenberg, GD, Sklar, P, State, MW, Sutcliffe, JS, Walsh, CA, Scherer, SW, Zwick, ME, Barett, JC, Cutler, DJ, Roeder, K, Devlin, B, Daly, MJ, Buxbaum, JD, De Rubeis, S, He, X, Goldberg, AP, Poultney, CS, Samocha, K, Cicek, AE, Kou, Y, Liu, L, Fromer, M, Walker, S, Singh, T, Klei, L, Kosmicki, J, Shih-Chen, F, Aleksic, B, Biscaldi, M, Bolton, PF, Brownfeld, JM, Cai, J, Campbell, NG, Carracedo, A, Chahrour, MH, Chiocchetti, AG, Coon, H, Crawford, EL, Curran, SR, Dawson, G, Duketis, E, Fernandez, BA, Gallagher, L, Geller, E, Guter, SJ, Hill, RS, Ionita-Laza, J, Jimenz Gonzalez, P, Kilpinen, H, Klauck, SM, Kolevzon, A, Lee, I, Lei, I, Lei, J, Lehtimäki, T, Lin, C-F, Ma'ayan, A, Marshall, CR, McInnes, AL, Neale, B, Owen, MJ, Ozaki, N, Parellada, M, Parr, JR, Purcell, S, Puura, K, Rajagopalan, D, Rehnström, K, Reichenberg, A, Sabo, A, Sachse, M, Sanders, SJ, Schafer, C, Schulte-Rüther, M, Skuse, D, Stevens, C, Szatmari, P, Tammimies, K, Valladares, O, Voran, A, Li-San, W, Weiss, LA, Willsey, AJ, Yu, TW, Yuen, RKC, DDD Study, Homozygosity Mapping Collaborative for Autism, UK10K Consortium, Cook, EH, Freitag, CM, Gill, M, Hultman, CM, Lehner, T, Palotie, A, Schellenberg, GD, Sklar, P, State, MW, Sutcliffe, JS, Walsh, CA, Scherer, SW, Zwick, ME, Barett, JC, Cutler, DJ, Roeder, K, Devlin, B, Daly, MJ, and Buxbaum, JD
Abstract: The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.
Published: 2014

21. Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

Author: ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD, Heine, H. S>, Bassett, J., Miller, L., Bassett, A., Ivins, B. E., Lehous, D., Arhin, F. F., Parr, Jr., T. R., Moeck, G., ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD, Heine, H. S>, Bassett, J., Miller, L., Bassett, A., Ivins, B. E., Lehous, D., Arhin, F. F., Parr, Jr., T. R., and Moeck, G.
Abstract: The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. The potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against B. anthracis (MIC against Ames strain, 0.015 microg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. In postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of oritavancin of 5, 15, or 50 mg/kg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100% proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90% of control animals receiving ciprofloxacin at 30 mg/kg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development; a single i.v. dose of 50 mg/kg administered 42 h after challenge provided 56% proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mg/kg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20% of mice at 30 days; mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models., Pub. in Antimicrobial Agents an Chemotherapy, v52 n9, p3350-3357, Sep 2008. Sponsored in part by Defense Threat Reduction Agency, project no. 02-4-2c-013.
Published: 2008

22. LETTERS.

Author: SOLIN, DONNA H., MOORE, DON, WENDT, ROBERT L., STANLEY, DOROTHY, MORSE, S. F . B., WORDEMAN, HORTENSE C., FISHER, DAN, REDDICK JR., JIM, PARR JR., W. S., E. D., BUCKLE, JACK C., GITTINGS, JAMES A., LOEFF, TED, and DUCKWORTH, EDWARD G.
Subjects: WOMEN'S clothing design
Published: 1947

23. Glycopeptides and Lipoglycopeptides.

Author: Arhin, F. F., Belley, A., Far, A. Rafai, Lehoux, D., Moeck, G., and Parr Jr., T. R.
Published: 2012
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24. Methemoglobin in hypoxic rats

Author: Olander, C. P. and Parr, Jr, C. E.
Published: 1977
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25. Comparative analyses of Serratia spp. outer membrane porin proteins

Author: Hutsul, Joanne, primary, Worobec, Elizabeth, additional, Parr Jr., Tom R., additional, and Becker, Gerald W., additional
Published: 1993
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26. Linking Bisphosphonates to the Free Amino Groups in Fluoroquinolones: Preparation of Osteotropic Prodrugs for the Prevention of Osteomyelitis.

Author: Tom J. Houghton, Kelly S. E. Tanaka, Ting Kang, Evelyne Dietrich, Yanick Lafontaine, Daniel Delorme, Sandra S. Ferreira, Frederic Viens, Francis F. Arhin, Ingrid Sarmiento, Dario Lehoux, Ibtihal Fadhil, Karine Laquerre, Jing Liu, Valérie Ostiguy, Hugo Poirier, Gregory Moeck, Thomas R. Parr Jr., and Adel Rafai Far
Published: 2008
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27. Current practice in the management of Attention Deficit Disorder with Hyperactivity (ADHD)

Author: Parr JR, Ward A, and Inman S
Abstract: BACKGROUND: The management of Attention Deficit Disorder with Hyperactivity (ADHD) is controversial and guidance published by the National Institute for Clinical Excellence (NICE) suggests a multidisciplinary approach. METHODS: We evaluated the patterns of referral and techniques used in the diagnosis and management of ADHD in Wirral Health Authority by studying the case notes of 391 children diagnosed between 1994 and August 2000. RESULTS: The majority of cases were referred from Primary Care and the detected prevalence was 8/1000. Boys were diagnosed more frequently than girls (12 : 1) and the mean age at diagnosis was 8.7 years; girls were more likely to have been diagnosed prior to age 8. The use of behaviour rating questionnaires and school visits as an aid to diagnosis increased during the study period. Management by Child Psychiatry and Community Paediatric services was similar with stimulant medication prescribed in 91% of cases; Child Psychiatry services were more likely to give advice on behaviour management than Paediatric services. Twelve per cent of cases were managed by both services, or in joint Outpatient clinics. Outpatient follow-up was most likely to occur at six monthly intervals and required 1312 appointments per year. CONCLUSIONS: This study shows that the management of children with ADHD in Wirral Health Authority is compatible with NICE guidance. Attention Deficit Disorder with Hyperactivity is a significant burden on clinical services and long-term planning is required. [ABSTRACT FROM AUTHOR]
Published: 2003
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28. Effects of Inner-Membrane-Associated β-Lactamase on Penicillin-Binding Protein Assays.

Author: Parr, Jr., Thomas R., Chan, Lydia, and Bayer, Arnold S.
Published: 1988
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29. Direct continuous method for monitoring biofilm infection in a mouse model.

Author: Kadurugamuwa, Jagath L, Sin, Lin, Albert, Eddie, Yu, Jun, Francis, Kevin, DeBoer, Monica, Rubin, Michael, Bellinger-Kawahara, Carole, Parr Jr, T R, and Contag, Pamela R
Abstract: We have developed a rapid, continuous method for real-time monitoring of biofilms, both in vitro and in a mouse infection model, through noninvasive imaging of bioluminescent bacteria colonized on Teflon catheters. Two important biofilm-forming bacterial pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, were made bioluminescent by insertion of a complete lux operon. These bacteria produced significant bioluminescent signals for both in vitro studies and the development of an in vivo model, allowing effective real-time assessment of the physiological state of the biofilms. In vitro viable counts and light output were parallel and highly correlated (S. aureus r = 0.98; P. aeruginosa r = 0.99) and could be maintained for 10 days or longer, provided that growth medium was replenished every 12 h. In the murine model, subcutaneous implantation of the catheters (precolonized or postimplant infected) was well tolerated. An infecting dose of 10 (3) to 10 (5) CFU/catheter for S. aureus and P. aeruginosa resulted in a reproducible, localized infection surrounding the catheter that persisted until the termination of the experiment on day 20. Recovery of the bacteria from the catheters of infected animals showed that the bioluminescent signal corresponded to the CFU and that the lux constructs were highly stable even after many days in vivo. Since the metabolic activity of viable cells could be detected directly on the support matrix, nondestructively, and noninvasively, this method is especially appealing for the study of chronic biofilm infections and drug efficacy studies in vivo.
Published: 2003

30. Comparative in vitro activity of oritavancin against Staphylococcus aureus strains that are resistant, intermediate or heteroresistant to vancomycin.

Author: Arhin, Francis F., Sarmiento, Ingrid, Parr Jr, Thomas R., and Moeck, Gregory
Subjects: STAPHYLOCOCCUS aureus, VANCOMYCIN, DILUTION, THERAPEUTICS research, GLYCOPEPTIDES, ANTIBACTERIAL agents, THERAPEUTICS
Abstract: The article presents a study that compares the in vitro activity of oritavancin against Staphylococcus aureus strains. The isolates include vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-resistant S. aureus, and heteroresistant VISA which are compared with in vitro activity of oritavancin using broth microdilution methodology. Based on the in vitro data, the authors highlighted the potential of oritavancin as a candidate in the treatment of infections caused by S. aureus strains challenged by vancomycin therapy.
Published: 2009
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31. Soviet Combat Engineer Support.

Author: ARMY INST FOR ADVANCED RUSSIAN AND EAST EUROPEAN STUDIES AP0 NEW YORK 09053, Parr, Jr, Arthur J, ARMY INST FOR ADVANCED RUSSIAN AND EAST EUROPEAN STUDIES AP0 NEW YORK 09053, and Parr, Jr, Arthur J
Abstract: This paper examines Soviet combat engineer equipment, organization and tactical groupings, staff procedures, and support to defensive, offensive, movement and river crossing operations. Types of engineer equipment are reviewed and briefly described. Organizational tables are adapted from accepted U.S. sources and improved to provide additional detail and conformity with Soviet sources, resulting from an extensive review of Soviet military journals, 1974- 1978. The single most important source is the book, 'Engineer Support of Combined Arms Combat' by Pliaskin, Lysukhin and Ruvinskii (1972), as translated by the author of this paper.
Published: 1978

32. Molecular basis of the non-β-lactamase-mediated resistance to β-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada

Author: Clairoux, N., Picard, M., Brochu, A., Rousseau, N., Gourde, P., Beauchamp, D., Parr Jr, T. R., Bergeron, M. G., and Francois Malouin

33. Phosphate-selective porins from the outer membranes of fluorescent Pseudomonas sp.

Author: Poole, Keith, primary, Parr Jr., Thomas R., additional, and Hancock, Robert E. W., additional
Published: 1987
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34. Lipopolysaccharide composition of three strains of Haemophilus influenzae

Author: Parr Jr., Thomas R., primary and Bryan, L. E., additional
Published: 1984
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35. Brown--Vialetto--Van Laere syndrome: a neurodegenerative condition with variable course.

Author: Parr JR, Andrews M, Hilton-Jones D, Talbot K, and Jayawant S
Published: 2007

36. Epilepsy responds to vagus nerve stimulation in ring chromosome 20 syndrome.

Author: Parr JR, Pang K, Mollett A, Zaiwalla Z, Selway R, McCormick D, Jayawant S, and Alpman A
Published: 2006
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37. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

Author: Joana Almeida, Christian R. Marshall, Hakon Hakonarson, Bárbara Oliveira, Anthony J. Griswold, Jacob A. S. Vorstman, Bhooma Thiruvahindrapuram, Suma Jacob, Judith Conroy, Alistair T. Pagnamenta, Christelle Cabrol, Jeremy R. Parr, Daniel H. Geschwind, Nancy J. Minshew, Xiao Xu, Richard Anney, Sven Bölte, Zhuozhi Wang, Emily L. Crawford, Elsa Delaby, Margaret A. Pericak-Vance, Joachim Hallmayer, Jonathan L. Haines, Dalila Pinto, Susana Mouga, Alexander Kolevzon, Elena Bacchelli, Frederico Duque, Bernie Devlin, Latha Soorya, Cátia Café, Kirsty Wing, Jennifer K. Lowe, Ana Tryfon, Stephen J. Guter, Geraldine Dawson, Tiago R. Magalhaes, Anthony J. Bailey, Michael Gill, Peter Szatmari, Steven Gallinger, Marion Pilorge, James S. Sutcliffe, Bridget A. Fernandez, Herman van Engeland, Catalina Betancur, Guiomar Oliveira, Andrew Green, Eftichia Duketis, Bernadette Rogé, Ann Le Couteur, Evdokia Anagnostou, Michelle Cotterchio, Daniele Merico, Giovanna Pellecchia, Jonathan Green, Regina Regan, Jillian P. Casey, Guiqing Cai, Gerard D. Schellenberg, Jennifer L. Howe, Elena Maestrini, Andrew D. Paterson, L. Alison McInnes, Patrick Bolton, Edwin H. Cook, Richard Delorme, Lambertus Klei, Thomas Bourgeron, Gillian Baird, Christine M. Freitag, Beth A. Dombroski, Andreas G. Chiocchetti, Sabine M. Klauck, Susan E. Folstein, Mafalda Barbosa, Anthony P. Monaco, Marion Leboyer, Nadia Bolshakova, Fritz Poustka, Richard Holt, Kerstin Wittemeyer, Wendy Roberts, Lonnie Zwaigenbaum, Louise Gallagher, Susan G. McGrew, Joseph D. Buxbaum, Graham Casey, Simon Wallace, Catherine Lord, Sean Brennan, Robert Ziman, Alison K. Merikangas, John I. Nurnberger, Christopher Gillberg, Ellen M. Wijsman, Astrid M. Vicente, Inȇs C. Conceição, Sean Ennis, Patricia Jiménez González, Hilary Coon, Raphael Bernier, John R. Gilbert, Ann P. Thompson, Susanne Thomson, Agatino Battaglia, Maretha de Jonge, Michael L. Cuccaro, Catarina Correia, Veronica J. Vieland, Stephen W. Scherer, Pauline Chaste, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Friedman Brain Institute, The Mindich Child Health and Development Institute, The Icahn Institute for Genomics and Multiscale Biology, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Trinity College Dublin-St. James's Hospital, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), McLaughlin Centre, University of Toronto, BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Department of Neurology, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Department of Pathology, Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Department of Preventive Medicine, University of Southern California (USC), Department of Pediatrics, University of Alberta, School of Education, University of Birmingham [Birmingham], University of Oxford [Oxford]-Warneford Hospital, Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Institute for Biomedical Imaging and Life Science, University of Coimbra [Portugal] (UC), Vanderbilt University [Nashville], Center for Autism and the Developing Brain (CADB), Weill Medical College of Cornell University [New York], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institute of Health and Society, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), Child Developmental and Behavioral Unit, Hospital Nacional de Niños Dr Sáenz Herrera, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Manchester Academic Health Sciences Centre, Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Institute of Child Health, University College of London [London] (UCL), Memorial University of Newfoundland [St. John's], Disciplines of Genetics and Medicine, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Institute of Psychiatry, King‘s College London, Institute of psychiatry, University of Washington [Seattle], Paediatric Neurodisability, King‘s College London-King's Health Partners, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, University of British Columbia (UBC), Bloorview Research Institute, Division of Medical Genetics [Seattle], Departments of Biostatistics and Medicine, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Institute of Neuroscience [Newcastle] (ION), Institutes of Neuroscience and Health and Society, Indiana University School of Medicine, Indiana University System-Indiana University System, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Utah Autism Research Program, University of Utah Psychiatry Department, University of Miami School of Medicine, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford School of Medicine [Stanford], Institute for Juvenile Research, University of Illinois [Chicago] (UIC), Department of Neuroscience, Main funders of the Autism Genome Project: Autism Speaks (USA), the Health Research Board (Ireland, AUT/2006/1, AUT/2006/2, PD/2006/48), the Medical Research Council (UK), the Hilibrand Foundation (USA), Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research (CIHR), Autism Genome Project Consortium, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), University of Pennsylvania, University of Oxford-Warneford Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Betancur, Catalina, Instituto Nacional de Saude Dr Ricardo Jorge, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE - UMR 8587), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Università di Bologna [Bologna] (UNIBO), Mount Sinai Hospital (MSH), University of Toronto-The Hospital for Sick Children, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Gillberg Neuropsychiatry Centre, University of Gothenburg (GU), Stanford University Medical School, Stanford University School of Medicine [Stanford], Stanford University [Stanford], Université de Toulouse (UT)-Université de Toulouse (UT), Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, 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 LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, and Scherer SW.
Subjects: Male, INTELLECTUAL DISABILITY, pathways, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Bioinformatics, DUPLICATIONS, Intellectual disability, Gene Regulatory Networks, Genetics(clinical), Copy-number variation, 10. No inequality, Child, GDI1, Genetics (clinical), Sequence Deletion, COPY NUMBER VARIANTS, Genetics, gene networks, Copy Number Variation, 3. Good health, Pedigree, Fragile X syndrome, Multigene Family, Female, Metabolic Networks and Pathways, de novo, DNA Copy Number Variations, autism, Biology, rare CNV, PHENOTYPE ONTOLOGY, Article, Structural variation, mental disorders, medicine, Humans, ddc:610, FRAGILE-X-SYNDROME, GENOME-WIDE ASSOCIATION, Gene, [SDV.GEN]Life Sciences [q-bio]/Genetics, HDAC4, SETD5, medicine.disease, CHD2, inherited, STRUCTURAL VARIATION, DELETIONS, DE-NOVO MUTATIONS, Child Development Disorders, Pervasive, Autism
Abstract: International audience; 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.
Published: 2014
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38. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author: Anita Thapar, Lena Backlund, Lindsey Kent, Walter J. Muir, A. Jeremy Willsey, Sandra K. Loo, Michael Boehnke, Christa Lese Martin, Ania Korszun, Guiomar Oliveira, Veronica J. Vieland, Stephen W. Scherer, René S. Kahn, Darina Czamara, Jeremy R. Parr, Michael E. Goddard, Willem A. Nolen, Josep Antoni Ramos-Quiroga, Stephen Sanders, Karola Rehnstroem, Nelson B. Freimer, Erin N. Smith, Ann Olincy, Ingrid Melle, Myrna M. Weissman, James A. Knowles, William Byerley, Aravinda Chakravarti, Shaun Purcell, Jens Treutlein, Sebastian Zoellner, Hakon Hakonarson, Susanne Lucae, Markus M. Noethen, Ian B. Hickie, Marion Friedl, Srinivasa Thirumalai, Stephen Newhouse, Joseph Piven, Andrew M. McIntosh, Cathryn M. Lewis, Srdjan Djurovic, Francis J. McMahon, Ayman H. Fanous, Bernie Devlin, Steven A. McCarroll, Alan F. Schatzberg, Peter Szatmari, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Gerard van Grootheest, Phil Lee, Richard Anney, Elaine K. Green, Geraldine Dawson, Joseph A. Sergeant, Digby Quested, Magdalena Gross, Jack D. Barchas, Nicholas G. Martin, Timothy W. Yu, Jouke-Jan Hottenga, Mark Lathrop, Federica Tozzi, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Sandra Meier, Louise Gailagher, David A. Collier, Farooq Amin, Michael C. Neale, Martin Schalling, Lieuwe de Haan, Bru Cormand, Falk W. Lohoff, Jennifer Crosbie, Howard J. Edenberg, Aarno Palotie, Johannes H. Smit, Robert Freedman, Katherine Gordon-Smith, Michele L. Pergadia, Enda M. Byrne, Hans-Christoph Steinhausen, Benjamin M. Neale, Anjali K. Henders, Michele T. Pato, Manuel Mattheisen, Urban Ösby, Edward M. Scolnick, Evaristus A. Nwulia, Fritz Poustka, Gonneke Willemsen, Andrew C. Heath, David St. Cair, Emma M. Quinn, I. Nicol Ferrier, John R. Kelsoe, Vanessa Hus, Andrew McQuillin, John P. Rice, William M. McMahon, Joseph Biederman, Danyu Lin, Wolfgang Maier, Frans G. Zitman, Josephine Elia, Nicholas J. Schork, Stéphane Jamain, Lizzy Rossin, Jubao Duan, Ingrid Agartz, Devin Absher, Jordan W. Smoller, Matthew W. State, Richard M. Myers, Shrikant Mane, Carlos N. Pato, William E. Bunney, Marian L. Hamshere, Manfred Uhr, Nicholas John Craddock, Astrid M. Vicente, Tobias Banaschewski, David Curtis, Anne Farmer, Scott D. Gordon, Anna K. Kaehler, Eric M. Morrow, Marcella Rietschel, Patrik K. E. Magnusson, Klaus-Peter Lesch, Rebecca McKinney, Jana Strohmaier, Thomas F. Wienker, Pablo V. Gejman, Douglas Blackwood, Maria Helena Pinto de Azevedo, Tiffany A. Greenwood, Don H. Linszen, Daniel L. Koller, Richard Bruggeman, Vinay Puri, Naomi R. Wray, Stanley J. Watson, Elena Maestrini, Valentina Moskvina, Frank Dudbridge, Danielle Posthuma, Edward G. Jones, Lambertus Klei, Sarah E. Bergen, Fan Meng, Steven P. Hamilton, Guy A. Rouleau, Pierandrea Muglia, Mikael Landén, Stephanie H. Witt, Laramie E. Duncan, Stanley Zammit, Judith A. Badner, Florian Holsboer, Eco J. C. de Geus, Daniel Moreno-De-Luca, Benjamin S. Pickard, Gunnar Morken, Michael Conlon O'Donovan, Michael Steffens, Kathryn Roeder, Dorret I. Boomsma, Paul D. Shilling, Stephan Ripke, Nigel Williams, Jeremy M. Silverman, David Craig, Mark J. Daly, Michael Bauer, Detelina Grozeva, Markus J. Schwarz, Peter Holmans, Hugh Gurling, T. Scott Stroup, Aribert Rothenberger, Gary Donohoe, Eric Fombonne, Joseph D. Buxbaum, Matthew Flicldnger, Bryan J. Mowry, Thomas Hansen, Ina Giegling, Grant W. Montgomery, Caroline M. Nievergelt, Susan L. Smalley, Jung-Ying Tzeng, David H. Ledbetter, Christopher A. Walsh, Gerard D. Schellenberg, Sarah E. Medland, Robert D. Oades, James B. Potash, Dan E. Arking, Johannes Schumacher, Michael Gill, James J. McGough, Jennifer L. Moran, Donald W. Black, Sian Caesar, Neelroop N. Parikshak, Ian W. Craig, Sabine M. Klauck, Wade H. Berrettini, T. Foroud, Peter P. Zandi, Inez Myin-Germeys, Marcus Ising, Sven Cichon, Alexandre A. Todorov, Mònica Bayés, Thomas Werge, Susan L. Slager, Stanley I. Shyn, Jim van Os, Derek W. Morris, Douglas M. Ruderfer, Thomas W. Muehleisen, Matthew C. Keller, Susmita Datta, Ian Jones, John B. Vincent, James L. Kennedy, Anthony P. Monaco, Jianxin Shi, Dale R. Nyholt, Bruno Etain, Christine Fraser, Paul Cormican, Miguel Casas, Radhika Kandaswamy, Gerome Breen, Stephen V. Faraone, Jonna Kuntsi, Thomas Bettecken, Witte J.G. Hoogendijk, Nancy G. Buccola, Franziska Degenhardt, Lyudmila Georgieva, Marion Leboyer, Alan R. Sanders, John Strauss, Dan Rujescu, Russell Schachar, Helena Medeiros, Lisa Jones, Peter M. Visscher, Lauren A. Weiss, René Breuer, John I. Nurnberger, Andreas Reif, Phoenix Kwan, Vihra Milanova, Chunyu Liu, Martin A. Kohli, Donald J. MacIntyre, Nicholas Bass, Khalid Choudhury, Edwin H. Cook, Catherine Lord, Andrew D. Paterson, Jobst Meyer, Richard P. Ebstein, Zhaoming Zhao, Niklas Laengstroem, Thomas G. Schulze, Peter Propping, Wei Xu, Robert C. Thompson, Kimberly Chambert, Jonathan Pimm, Ivan Nikolov, Pamela A. F. Madden, Kevin A. McGhee, Jacob Lawrence, Jan K. Buitelaar, Andres Ingason, Christine M. Freitag, Robert Krasucki, Wiepke Cahn, Rita M. Cantor, Christina M. Hultman, Melvin G. McInnis, Catalina Betancur, Eftichia Duketis, Michael T. Murtha, Thomas H. Wassink, Philip Asherson, John S. Witte, Elaine Kenny, Edmund J.S. Sonuga-Barke, Lydia Krabbendam, Line Olsen, Agatino Battaglia, Laura J. Scott, Annette M. Hartmann, Yunjung Kim, Richard O. Day, Edwin J. C. G. van den Oord, Ole A. Andreassen, Herbert Roeyers, Michael John Owen, Colm O'Dushlaine, Peng Zhang, Morten Mattingsdal, Michael L. Cuccaro, Margaret A. Pericak-Vance, Joachim Hallmayer, Jun Li, Pamela B. Mahon, Elisabeth B. Binder, William A. Scheftner, Daniel H. Geschwind, Christel M. Middeldorp, Josef Frank, Keith Matthews, Jennifer K. Lowe, Paul Lichtenstein, Verneri Anttila, Pamela Sklar, Szabocls Szelinger, Roel A. Ophoff, Peter McGuffin, Stefan Herms, Bettina Konte, George Kirov, Hilary Coon, Maria Hipolito, Louise Frisén, Kenneth S. Kendler, Frank Bellivier, James S. Sutdiffe, Jeffrey A. Lieberman, Todd Lencz, Susanne Hoefels, Alan W. McLean, Barbara Franke, Huda Akil, Soumya Raychaudhuri, Ellen M. Wijsman, Vishwajit L. Nimgaonkar, Roy H. Perlis, Patrick J. McGrath, Susan L. Santangelo, William Coryell, Henrik B. Rasmussen, Weihua Guan, William Lawson, Elliot S. Gershon, Sean Ennis, Aiden Corvin, Allan H. Young, Thomas B. Barrett, Jonathan L. Haines, Douglas F. Levinson, Ana Miranda, Anil K. Malhotra, S. Hong Lee, Stan F. Nelson, Anthony J. Bailey, Patrick F. Sullivan, Dorothy E. Grice, Lefkos T. Middleton, Bertram Mueller-Myhsok, Michael R. Barnes, Adebayo Anjorin, O'Dushlaine, C, Rossin, L, Lee, Ph, Duncan, L, Parikshak, Nn, Newhouse, S, Ripke, S, Neale, Bm, Purcell, Sm, Posthuma, D, Nurnberger, Ji, Lee, Sh, Faraone, Sv, Perlis, Rh, Mowry, Bj, Thapar, A, Goddard, Me, Witte, J, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, Oa, Anjorin, A, Anney, R, Anttila, V, Arking, De, Asherson, P, Azevedo, Mh, Backlund, L, Badner, Ja, Bailey, Aj, Banaschewski, T, Barchas, Jd, Barnes, Mr, Barrett, Tb, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, Se, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, Eb, Black, Dw, Blackwood, Dh, Bloss, C, Boehnke, M, Boomsma, Di, Breuer, R, Bruggeman, R, Cormican, P, Buccola, Ng, Buitelaar, Jk, Bunney, We, Buxbaum, Jd, Byerley, Wf, Byrne, Em, Caesar, S, Cahn, W, Cantor, Rm, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Mattheisen, M, Cloninger, Cr, Collier, Da, Cook, Eh, Coon, H, Cormand, B, Corvin, A, Coryell, Wh, Craig, Dw, Craig, Iw, Crosbie, J, Cuccaro, Ml, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, Ej, Degenhardt, F, Djurovic, S, Donohoe, Gj, Doyle, Ae, Duan, J, Dudbridge, F, Duketis, E, Ebstein, Rp, Edenberg, Hj, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, Ae, Ferrier, In, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, Nb, Freitag, Cm, Friedl, M, Frisén, L, Gallagher, L, Gejman, Pv, Georgieva, L, Gershon, E, Giegling, I, Gill, M, Gordon, Sd, Gordon-Smith, K, Green, Ek, Greenwood, Ta, Grice, De, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, Jl, Hakonarson, H, Hallmayer, J, Hamilton, Sp, Hamshere, Ml, Hansen, Tf, Hartmann, Am, Hautzinger, M, Heath, Ac, Henders, Ak, Herms, S, Hickie, Ib, Hipolito, M, Hoefels, S, Holsboer, F, Hoogendijk, Wj, Hottenga, Jj, Hultman, Cm, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, Eg, Jones, I, Jones, L, Tzeng, Jy, Kähler, Ak, Kahn, R, Kandaswamy, R, Keller, Mc, Kennedy, Jl, Kenny, E, Kent, L, Kim, Y, Kirov, Gk, Klauck, Sm, Klei, L, Knowles, Ja, Kohli, Ma, Koller, Dl, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landén, M, Längström, N, Lathrop, M, Lawrence, J, Lawson, Wb, Leboyer, M, Ledbetter, Dh, Lencz, T, Lesch, Kp, Levinson, Df, Lewis, Cm, Li, J, Lichtenstein, P, Lieberman, Ja, Lin, Dy, Linszen, Dh, Liu, C, Lohoff, Fw, Loo, Sk, Lord, C, Lowe, Jk, Lucae, S, Macintyre, Dj, Madden, Pa, Maestrini, E, Magnusson, Pk, Mahon, Pb, Maier, W, Malhotra, Ak, Mane, Sm, Martin, Cl, Martin, Ng, Matthews, K, Mattingsdal, M, Mccarroll, Sa, Mcghee, Ka, Mcgough, Jj, Mcgrath, Pj, Mcguffin, P, Mcinnis, Mg, Mcintosh, A, Mckinney, R, Mclean, Aw, Mcmahon, Fj, Mcmahon, Wm, Mcquillin, A, Medeiros, H, Medland, Se, Meier, S, Melle, I, Meyer, J, Middeldorp, Cm, Middleton, L, Milanova, V, Miranda, A, Monaco, A, Montgomery, Gw, Moran, Jl, Moreno-De-Luca, D, Morken, G, Morris, Dw, Morrow, Em, Moskvina, V, Muglia, P, Mühleisen, Tw, Muir, Wj, Müller-Myhsok, B, Murtha, M, Myers, Rm, Myin-Germeys, I, Neale, Mc, Nelson, Sf, Nievergelt, Cm, Nikolov, I, Nimgaonkar, V, Nolen, Wa, Nöthen, Mm, Nwulia, Ea, Nyholt, Dr, Oades, Rd, Olincy, A, Oliveira, G, Olsen, L, Ophoff, Ra, Osby, U, Owen, Mj, Palotie, A, Parr, Jr, Paterson, Ad, Pato, Cn, Pato, Mt, Penninx, Bw, Pergadia, Ml, Pericak-Vance, Ma, Pickard, B, Pimm, J, Piven, J, Potash, Jb, Poustka, F, Propping, P, Puri, V, Quested, Dj, Quinn, Em, Ramos-Quiroga, Ja, Rasmussen, Hb, Raychaudhuri, S, Rehnström, K, Reif, A, Ribasés, M, Rice, Jp, Rietschel, M, Roeder, K, Roeyers, H, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, Ar, Sanders, Sj, Santangelo, Sl, Sergeant, Ja, Schachar, R, Schalling, M, Schatzberg, Af, Scheftner, Wa, Schellenberg, Gd, Scherer, Sw, Schork, Nj, Schulze, Tg, Schumacher, J, Schwarz, M, Scolnick, E, Scott, Lj, Shi, J, Shilling, Pd, Shyn, Si, Silverman, Jm, Slager, Sl, Smalley, Sl, Smit, Jh, Smith, En, Sonuga-Barke, Ej, St Clair, D, State, M, Steffens, M, Steinhausen, Hc, Strauss, J, Strohmaier, J, Stroup, T, Sutcliffe, J, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, Rc, Todorov, Aa, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, Jc, Van Grootheest, G, Van Os, J, Vicente, A, Vieland, Vj, Vincent, Jb, Visscher, Pm, Walsh, Ca, Wassink, Th, Watson, Sj, Weissman, Mm, Werge, T, Wienker, Tf, Wijsman, Em, Willemsen, G, Williams, N, Willsey, Aj, Witt, Sh, Xu, W, Young, Ah, Yu, Tw, Zammit, S, Zandi, Pp, Zhang, P, Zitman, Fg, Zöllner, S, Devlin, B, Kelsoe, Jr, Sklar, P, Daly, Mj, O'Donovan, Mc, Craddock, N, Kendler, K, Weiss, La, Wray, Nr, Zhao, Z, Geschwind, Dh, Sullivan, Pf, Smoller, Jw, Holmans, Pa, Breen, G., Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Human genetics, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Gastroenterology & Hepatology, Hematology, University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), RS: MHeNs - R2 - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Universitat de Barcelona, Perceptual and Cognitive Neuroscience (PCN), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Complex Trait Genetics, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, LEARN! - Brain, learning and development, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Lee, S Hong, Breen, Gerome, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, and Myin-Germeys, Inez
Subjects: Netherlands Twin Register (NTR), Statistical methods, Autism, Medizin, LOCI, Genome-wide association study, heritability, Genome-wide association studies, Histones, Genètica mèdica, 0302 clinical medicine, Histone methylation, Databases, Genetic, 2.1 Biological and endogenous factors, Psychology, GWAS, Aetiology, Psychiatric genetics, R2C, bipolar disorder, Psychiatry, 0303 health sciences, Disorders, Loci, Depression, General Neuroscience, Mental Disorders, Medical genetics, METHYLATION, Brain, 3rd-DAS, Serious Mental Illness, Psychiatric Disorders, 3. Good health, Histone, Mental Health, Schizophrenia, Mental Disorder, Cognitive Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Promoters, BDC, BURDEN, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Human, Signal Transduction, medicine.medical_specialty, DISORDERS, Genomics, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Burden, Biology, Methylation, Article, Biological pathway, PROMOTERS, 03 medical and health sciences, Databases, Genetic, medicine, Genetics, Humans, Genetic Predisposition to Disease, histone methylation, Bipolar disorder, Psiquiatria, AUTISM, 030304 developmental biology, Genetic association, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Human Genome, Neurosciences, medicine.disease, Brain Disorders, Good Health and Well Being, DE-NOVO MUTATIONS, Perturbações do Desenvolvimento Infantil e Saúde Mental, RC0321, Genome-wide Association Studies, De-novo mutations, major depression, Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. Postprint
Published: 2015
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39. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Author: Laura J. Scott, Bernie Devlin, Steven A. McCarroll, James S. Sutcliffe, Stefan Herms, Yunjung Kim, Richard O. Day, Thomas F. Wienker, Frank Dudbridge, I. Nicol Ferrier, Bettina Konte, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Detelina Grozeva, Herbert Roeyers, Peter Holmans, Colm O'Dushlaine, Scott D. Gordon, Sarah E. Bergen, Fan Meng, Morten Mattingsdal, Hugh Gurling, Ina Giegling, Gerard van Grootheest, Ania Korszun, Markus J. Schwarz, George Kirov, Sebastian Zöllner, Kenneth S. Kendler, Nicholas G. Martin, Michael Conlon O'Donovan, Michael C. Neale, Jim van Os, Aravinda Chakravarti, Timothy W. Yu, Mikael Landén, Inez Myin-Germeys, Markus M. Nöthen, Kathryn Roeder, James B. Potash, Alan W. McLean, Louise Gallagher, Anna K. Kähler, Thomas Bettecken, Nigel Williams, Frank Bellivier, Joseph D. Buxbaum, Derek W. Morris, Susan L. Smalley, Jung-Ying Tzeng, Martin Schalling, Douglas M. Ruderfer, Caroline M. Nievergelt, T. Scott Stroup, David H. Ledbetter, Jennifer Crosbie, Anita Thapar, Barbara Franke, Jeffrey A. Lieberman, Huda Akil, Miguel Casas, Daniel H. Geschwind, Paul Cormican, Bertram Müller-Myhsok, Lyudmila Georgieva, Robert Krasucki, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Gerard D. Schellenberg, Todd Lencz, Melvin G. McInnis, Catalina Betancur, Josep Antoni Ramos-Quiroga, Stephen Sanders, Eftichia Duketis, Don H. Linszen, Matthew W. State, Richard M. Myers, Soumya Raychaudhuri, Lizzy Rossin, Howard J. Edenberg, Michael E. Goddard, S. Hong Lee, Elisabeth B. Binder, Pablo V. Gejman, William A. Scheftner, Wolfgang Maier, Judith A. Badner, Christel M. Middeldorp, Maria Helena Pinto de Azevedo, Johannes H. Smit, Willem A. Nolen, Lieuwe de Haan, Gonneke Willemsen, Keith Matthews, Ellen M. Wijsman, Jennifer K. Lowe, Rebecca McKinney, Magdalena Gross, Dorothy E. Grice, James A. Knowles, Andrew C. Heath, Jana Strohmaier, Vishwajit L. Nimgaonkar, William Byerley, William E. Bunney, Dan E. Arking, Andrew McQuillin, William M. McMahon, Manuel Mattheisen, Hans-Christoph Steinhausen, Joseph Biederman, Guy A. Rouleau, James J. McGough, Sian Caesar, Edward M. Scolnick, Lefkos T. Middleton, Jack D. Barchas, Ian B. Hickie, Danyu Lin, Patrik K. E. Magnusson, Douglas Blackwood, Francis J. McMahon, Ingrid Agartz, Elena Maestrini, Marian L. Hamshere, Lindsey Kent, Walter J. Muir, Stephan Ripke, Lydia Krabbendam, Christine Fraser, Maria Hipolito, Louise Frisén, Eric Fombonne, Emma M. Quinn, Michael Bauer, Richard P. Ebstein, Michael Steffens, Jordan W. Smoller, Stanley J. Watson, Michael Boehnke, Philip Asherson, Agatino Battaglia, Elliot S. Gershon, Russell Schachar, Marcus Ising, Peng Zhang, Margaret A. Pericak-Vance, Joachim Hallmayer, Sean Ennis, Radhika Kandaswamy, René S. Kahn, Susanne Hoefels, Thomas W. Mühleisen, Pamela Sklar, Paul Lichtenstein, Verneri Anttila, Michael L. Cuccaro, Florian Holsboer, René Breuer, Eric M. Morrow, Vinay Puri, Naomi R. Wray, Szabocls Szelinger, Sabine M. Klauck, John B. Vincent, Shrikant Mane, Aribert Rothenberger, Marion Friedl, Ian Jones, Khalid Choudhury, Michael R. Barnes, Adebayo Anjorin, Edwin H. Cook, William Lawson, Allan H. Young, Lambertus Klei, Bryan J. Mowry, Johannes Schumacher, Michael Gill, James L. Kennedy, Marcella Rietschel, Aiden Corvin, Henrik B. Rasmussen, Susmita Datta, Kimberly Chambert, Daniel Moreno-De-Luca, Benjamin S. Pickard, Stan F. Nelson, Veronica J. Vieland, Stephen W. Scherer, Peter M. Visscher, John Strauss, Andreas Reif, Andrew D. Paterson, Ann Olincy, Phoenix Kwan, Anthony J. Bailey, Patrick F. Sullivan, Pierandrea Muglia, Gunnar Morken, Susanne Lucae, Ayman H. Fanous, Jacob Lawrence, Donald J. MacIntyre, Nancy G. Buccola, Rita M. Cantor, Christina M. Hultman, Weihua Guan, Anthony P. Monaco, Jouke-Jan Hottenga, Elaine Kenny, Jianxin Shi, Dale R. Nyholt, Kevin A. McGhee, Falk W. Lohoff, Jonna Kuntsi, Niklas Långström, John I. Nurnberger, Nelson B. Freimer, Erin N. Smith, John P. Rice, Michael T. Murtha, Thomas H. Wassink, Alexandre A. Todorov, Edmund J.S. Sonuga-Barke, Dan Rujescu, Roy H. Perlis, John S. Witte, Christopher A. Walsh, Matthew C. Keller, Pamela B. Mahon, Patrick J. McGrath, Susan L. Santangelo, Annette M. Hartmann, Ole A. Andreassen, Tatiana Foroud, Shaun Purcell, Josef Frank, Douglas F. Levinson, William Coryell, Ana Miranda, Alan F. Schatzberg, Peter Szatmari, Jun Li, Gerome Breen, Stephen V. Faraone, Anil K. Malhotra, Helena Medeiros, Martin A. Kohli, Nicholas Bass, Catherine Lord, Peter Propping, Wei Xu, Federica Tozzi, Ivan Nikolov, Jan K. Buitelaar, Thomas G. Schulze, Katherine Gordon-Smith, Michele L. Pergadia, Fritz Poustka, Valentina Moskvina, David Curtis, Tobias Banaschewski, Devin Absher, Danielle Posthuma, Stanley Zammit, Gary Donohoe, Ingrid Melle, Karola Rehnström, Thomas Hansen, Myrna M. Weissman, Stanley I. Shyn, Hakon Hakonarson, Christa Lese Martin, Digby Quested, Darina Czamara, Jeremy R. Parr, Pamela A. F. 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Greenwood, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Lee, S Hong, Ripke, Stephan, Neale, Benjamin M, Faraone, Stephen V, Wray, Naomi R, Cross-Disorder Group of the Psychiatric Genomics Consortium, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Queensland Brain Institute, University of Queensland [Brisbane], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], SUNY Upstate Medical University, State University of New York (SUNY), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Psychiatric and Neurodevelopmental Genetics Unit, Queensland Centre for Mental Health Research, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], New South Wales Department of Primary Industries (NSW DPI), Faculty of Land and Food Resources, University of Melbourne, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Diakonhjemmet Hospital, University of Michigan [Ann Arbor], University of Michigan System, Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan System-University of Michigan System, Emory University [Atlanta, GA], Oslo University Hospital [Oslo], University College of London [London] (UCL), Trinity College Dublin, Johns Hopkins University School of Medicine [Baltimore], MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King's College London, University of Coimbra [Portugal] (UC), Karolinska Institutet [Stockholm], University of Chicago, University of British Columbia (UBC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Weill Medical College of Cornell University [New York], GlaxoSmithKline, Glaxo Smith Kline, Portland Veterans Administration Medical Center, Windeyer Institute for Medical Sciences, IRCCS Fondazione Stella Maris [Pisa], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Department of Psychiatry [Philadelphia], University of Pennsylvania, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Massachusetts General Hospital [Boston, MA, USA], University of Iowa [Iowa City], University of Edinburgh, Royal Hospital for Sick Children [Edinburgh], The Scripps Research Institute [La Jolla, San Diego], MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Institute of Medical Sciences, University of Aberdeen, Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, Department of Psychiatry, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Trinity College Dublin-St. James's Hospital, School of Nursing, Louisiana State University (LSU), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Department of Psychiatry and Human Behavior, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Department of Neuroscience, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Friedman Brain Institute, The Mindich Child Health and Development Institute, University of California [San Francisco] (UC San Francisco), Department of Psychiatry, School of Clinical and Experimental Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Mental Health Sciences Unit, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Developmental Neuroscience, Neuropsychiatric Genetics Research Group, University of California [San Diego] (UC San Diego), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], East London NHS Foundation Trust, Queen Mary University of London (QMUL), Max-Planck-Institut für Psychiatrie, Genetics Institute, Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Medstar Research Institute, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry and Behavioral Sciences, University of Chicago-NorthShore University Health System, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Psychology Department, National University of Singapore (NUS), Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - 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Keck Biotechnology Resource Laboratory, Yale University [New Haven], Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Genetic Epidemiology Unit, Queensland Institute of Medical Research, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Sorlandet Hospital HF, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Medical Genetics Section, University of Edinburgh-Western General Hospital, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Division of Mental Health and Addiction, Molecular Psychiatry Laboratory, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Research and Development, First Psychiatric Clinic-Alexander University Hospital, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, St. Olav's Hospital, Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Human Genetics Department, University of Pittsburgh (PITT), Institute for Biomedical Imaging and Life Science, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Carolina Institute for Developmental Disabilities, Analytic and Translational Genetics Unit, Rush University Medical Center [Chicago], Julius-Maximilians-Universität Würzburg (JMU), Washington University in Saint Louis (WUSTL), Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Department of Experimental Clinical and Health Psychology, Universiteit Gent = Ghent University (UGENT), Department of Child and Adolescent Psychiatry, Georg-August-University = Georg-August-Universität Göttingen, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Departments of Psychiatry and Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Maine Medical Center, Free University of Amsterdam, Department of Psychiatry and Behavioral Sciences [Stanford], Pathology and Laboratory Medicine, The Scripps Translational Science Institute and The Scripps Research Institute, Psychiatric Center Nordbaden, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), The Scripps Translational Science Institute and Scripps Health, Child and Adolescent Psychiatry, Aarhus University Hospital, Molecular Neuropsychiatry and Development Laboratory, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Translational Genomics Research Institute (TGen), Oxford Health NHS Foundation Trust, Marlborough House Secure Unit, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, University of Toronto, Diamantina Institute, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, University of Washington [Seattle], ArcelorMittal Maizières Research SA, ArcelorMittal, Institute of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, LEARN! - Brain, learning and development, EMGO+ - Mental Health, LEARN!, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, State University of New York (SUNY)-State University of New York (SUNY), Department of Neuroscience and Physiology, Faculty of Land and Environment, Biosciences Research Division, Department of Environment and Primary Industries Victoria, Department of Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), University of California-University of California, Universität Heidelberg [Heidelberg], Cornell University [New York]-Weill Medical College of Cornell University [New York], Bioinformatics, Internal Medicine, Portland Va Medical Center : Ganzini Linda MD, Technische Universität Dresden = Dresden University of Technology (TU Dresden)-University Hospital Carl Gustav Carus, Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of California [Irvine] (UCI), University of California-University of California-University of California [Los Angeles] (UCLA), University of Bonn, University of California-University of California-David Geffen School of Medicine [Los Angeles], Cardiff University-Medical Research Council, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Göttingen - Georg-August-Universität Göttingen, Yale University School of Medicine, Georg-August-University [Göttingen], ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK, Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O'Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR, Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A, Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ, Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF, Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ, O'Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR, Cardiff University-Medical Research Council (MRC), HudsonAlpha Institute for Biotechnology, The Institute of Psychiatry-King‘s College London, Cornell University-Weill Medical College of Cornell University [New York], Stanford University Medical School, Technische Universität Dresden (TUD)-University Hospital Carl Gustav Carus, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, McGill University-Montreal Children's Hospital, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Stanford University School of Medicine [Stanford], Stanford University [Stanford], Eberhard Karls Universität Tübingen, Friedrich Alexander University [Erlangen-Nürnberg], Università di Bologna [Bologna] (UNIBO), University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Washington University School of Medicine, Ghent University [Belgium] (UGENT), University of Goettingen, CHUM Research Center, Psychiatry and Behavioral Science, Stanford University School of Medicine [CA, USA], Aalborg Psychiatric Hospital, Aarhus University Hospital, Washington University in St Louis, Instituto Nacional de Saude Dr Ricardo Jorge, Oades, Robert D., Guellaen, Georges, Medical Oncology, Epidemiology, Child and Adolescent Psychiatry / Psychology, and Hematology
Subjects: Netherlands Twin Register (NTR), Medizin, Inheritance Patterns, Social Sciences, AUTISM SPECTRUM DISORDERS, nosology, heritability, COMMON SNPS, 0302 clinical medicine, Crohn Disease, SCHIZOPHRENIA, Child, Psychiatric genetics, Genetics & Heredity, MAJOR DEPRESSIVE DISORDER, RISK, 0303 health sciences, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, 120 000 Neuronal Coherence, Mental Disorders, Variants, BIPOLAR DISORDER, ASSOCIATION, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], Psychiatric Disorders, CROHNS-DISEASE, 3. Good health, Schizophrenia, genetic association study, Medical genetics, Major depressive disorder, SNPs, Adult, medicine.medical_specialty, genetic etiology, medical genetics, DEFICIT HYPERACTIVITY DISORDER, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], Heritability, Genetic Heterogeneity, 03 medical and health sciences, Prevalence of mental disorders, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, ddc:61, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DCN PAC - Perception action and control NCEBP 9 - Mental health, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Genome, Human, Genetic heterogeneity, medicine.disease, schizophrenia, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Published: 2013
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40. Individual common variants exert weak effects on the risk for autism spectrum disorderspi

Author: Naisha Shah, William M. McMahon, Barbara Parrini, Jeremy R. Parr, Thomas Bourgeron, Vanessa Hus, Gudrun Nygren, Sabine M. Klauck, John B. Vincent, Nadine M. Melhem, Jillian P. Casey, Christina Corsello, Jonathan L. Haines, Andrew D. Paterson, Raffaella Tancredi, Alistair T. Pagnamenta, Jonathan Green, Richard Delorme, Geraldine Dawson, Andrew Pickles, Carine Mantoulan, Alexander Kolevzon, Bridget A. Fernandez, Frederico Duque, Inês Sousa, Tara Paton, Kathryn Roeder, Joana Almeida, Richard Anney, Margaret A. Pericak-Vance, Joachim Hallmayer, Gerard D. Schellenberg, Sabata C. Lund, Rita M. Cantor, Daniel H. Geschwind, Janine A. Lamb, Annette Estes, Sven Bölte, Hakon Hakonarson, Gillian Hughes, Gillian Baird, John I. Nurnberger, Jessica Brian, Bernie Devlin, Roberta Igliozzi, Vera Stoppioni, Jiannis Ragoussis, Peter Szatmari, Ghazala Mirza, Eric Fombonne, Thomas H. Wassink, Emily L. Crawford, Nuala Sykes, Danielle Zurawiecki, Graham Kenny, David J. Posey, Elena Maestrini, Vlad Kustanovich, Elena Bacchelli, Veronica J. Vieland, Stephen W. Scherer, Guiomar Oliveira, Simon Wallace, John R. Gilbert, Latha Soorya, Sean Brennan, Tiago R. Magalhaes, Hilary Coon, Elizabeth A. Heron, Sabine Schlitt, Fritz Poustka, Astrid M. Vicente, Patrick Bolton, Linda Lotspeich, Nancy J. Minshew, Val C. Sheffield, Bennett L. Leventhal, Xiao-Qing Liu, Andrew Green, Joseph D. Buxbaum, Shawn Wood, Susan E. Folstein, Sean Ennis, Catarina Correia, James S. Sutcliffe, Carolyn Noakes, Ann Le Couteur, Marion Leboyer, Ann P. Thompson, Christine M. Freitag, Fred R. Volkmar, Katerina Papanikolaou, Dalila Pinto, Agatino Battaglia, Frances Lombard, Joseph Piven, Maretha de Jonge, Michael Rutter, Clara Lajonchere, Kerstin Wittemeyer, Herman van Engeland, Michael L. Cuccaro, Richard Holt, Lonnie Zwaigenbaum, Louise Gallagher, Jeff Munson, Ana Tryfon, John Tsiantis, Lambertus Klei, Christopher Gillberg, Penny Farrar, Joseph T. Glessner, Ellen M. Wijsman, Anthony P. Monaco, Wendy Roberts, Nadia Bolshakova, Cecilia Kim, Judith Miller, Stephen J. Guter, Susanne Thomson, Catherine Lord, Anthony J. Bailey, Miriam Law-Smith, Michael Gill, Christopher J. McDougle, Bernadette Rogé, Alison K. Merikangas, Jacob A. S. Vorstman, Suma Jacob, Judith Conroy, Kirsty Wing, Regina Regan, Jennifer L. Howe, Stanley F. Nelson, Edwin H. Cook, Catalina Betancur, Eftichia Duketis, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Centre for Applied Genomics, Toronto, University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Newcomen Centre, Guy's Hospital [London], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Department of Child and Adolescent Psychiatry, Institute of psychiatry, Molecular and Cellular Neurobiology, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Disciplines of Genetics and Medicine, Memorial University of Newfoundland [St. John's], University of Miami School of Medicine, John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Research Unit on Children's Psychosocial Maladjustment, Université Laval [Québec] (ULaval)-Department of Psychology, University of Gothenburg (GU), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Manchester Academic Health Sciences Centre, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Autism Genetic Resource Exchange, Autism Speaks, Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Centre de Référence du Syndrome de Prader-Willi, CHU Toulouse [Toulouse], Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Psychiatry and Behavioral Sciences, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Social, Genetic and Developmental Psychiatry Centre, Department of Pediatrics, University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Neuropsichiatria Infantile, Ospedale Santa Croce, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, University of Toronto, Child Study Centre, Yale University School of Medicine, University of Oxford [Oxford]-Warneford Hospital, University of Alberta, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California-University of California [Los Angeles] (UCLA), University of California-University of California, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Carolina Institute for Developmental Disabilities, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stanford School of Medicine [Stanford], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Children’s Hospital of Philadelphia (CHOP )-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Yale School of Medicine [New Haven, Connecticut] (YSM), King‘s College London-The Institute of Psychiatry, University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Anney R, Klei L, Pinto D, Almeida J, Bacchelli E, Baird G, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Casey J, Conroy J, Correia C, Corsello C, Crawford EL, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Gilbert J, Gillberg C, Glessner JT, Green A, Green J, Guter SJ, Heron EA, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Jacob S, Kenny GP, Kim C, Kolevzon A, Kustanovich V, Lajonchere CM, Lamb JA, Law-Smith M, Leboyer M, Le Couteur A, Leventhal BL, Liu XQ, Lombard F, Lord C, Lotspeich L, Lund SC, Magalhaes TR, Mantoulan C, McDougle CJ, Melhem NM, Merikangas A, Minshew NJ, Mirza GK, Munson J, Noakes C, Nygren G, Papanikolaou K, Pagnamenta AT, Parrini B, Paton T, Pickles A, Posey DJ, Poustka F, Ragoussis J, Regan R, Roberts W, Roeder K, Roge B, Rutter ML, Schlitt S, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Sykes N, Tancredi R, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman J, Wallace S, Wing K, Wittemeyer K, Wood S, Zurawiecki D, Zwaigenbaum L, Bailey AJ, Battaglia A, Cantor RM, Coon H, Cuccaro ML, Dawson G, Ennis S, Freitag CM, Geschwind DH, Haines JL, Klauck SM, McMahon WM, Maestrini E, Miller J, Monaco AP, Nelson SF, Nurnberger JI Jr, Oliveira G, Parr JR, Pericak-Vance MA, Piven J, Schellenberg GD, Scherer SW, Vicente AM, Wassink TH, Wijsman EM, Betancur C, Buxbaum JD, Cook EH, Gallagher L, Gill M, Hallmayer J, Paterson AD, Sutcliffe JS, Szatmari P, Vieland VJ, Hakonarson H, Devlin B, University of Oxford, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Oxford-Warneford Hospital, University of Pennsylvania, University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Betancur, Catalina, and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: Male, CNTNAP2, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Nerve Tissue Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Language Development, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, autism spectrum disorders (ASDs), Gene Frequency, Risk Factors, mental disorders, Genetics, medicine, Humans, Genetic Predisposition to Disease, Copy-number variation, Allele, GENOME-WIDE ASSOCIATION, Child, Molecular Biology, Allele frequency, Genetics (clinical), Alleles, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Association Studies Articles, Membrane Proteins, General Medicine, medicine.disease, Genetic architecture, Child Development Disorders, Pervasive, common variant, Perturbações do Desenvolvimento Infantil e Saúde Mental, Autism, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: International audience; While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Published: 2012
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41. A genome-wide scan for common alleles affecting risk for autism

Author: Veronica J. Vieland, Stephen W. Scherer, Elizabeth A. Heron, Barbara Parrini, Jeremy R. Parr, Louise Gallagher, Jeff Munson, Annemarie Poustka, Susan E. Folstein, Irene Drmic, Gudrun Nygren, John P. Rice, Jeff Salt, Simon Wallace, Geraldine Dawson, Daniel H. Geschwind, Annette Estes, Sean Brennan, Alistair T. Pagnamenta, Nancy J. Minshew, Christina Corsello, Jonathan Green, William M. McMahon, Christopher Gillberg, Kathryn Roeder, Lambertus Klei, Anath C. Lionel, Bridget A. Fernandez, Thomas Bourgeron, Ellen M. Wijsman, Gerard D. Schellenberg, Wendy Roberts, Jeremy Goldberg, Frederico Duque, Ghazala Mirza, Sean Ennis, Joana Almeida, Nadine M. Melhem, Jillian P. Casey, Roberta Igliozzi, Ricardo Segurado, Carine Mantoulan, Katy Renshaw, Kai Wang, Andrew D. Paterson, Raffaella Tancredi, Matthew Nicholas Hill, Richard Anney, Christian R. Marshall, Anthony P. Monaco, Linda Lotspeich, Marion Leboyer, Richard Holt, Andrew Pickles, Vlad Kustanovich, William M. Mahoney, Jessica Brian, Inês Sousa, Peter Szatmari, Vanessa Hus, Janine A. Lamb, Hakon Hakonarson, Lonnie Zwaigenbaum, John Tsiantis, David J. Posey, Olena Korvatska, Guillermo Casallo, Rita M. Cantor, Bhooma Thiruvahindrapduram, Nadia Bolshakova, Sven Bölte, Alison K. Merikangas, Brian L. Yaspan, Cecilia Kim, Andrew Crossett, Fritz Poustka, Danielle Zurawiecki, Agatino Battaglia, Sabata C. Lund, Ann P. Thompson, Bennett L. Leventhal, Jessica Rickaby, Zhouzhi Wang, John I. Nurnberger, Astrid M. Vicente, Maretha de Jonge, Tiago R. Magalhaes, Michael L. Cuccaro, Val C. Sheffield, Nuala Sykes, Elena Maestrini, Guiomar Oliveira, Joseph D. Buxbaum, Fred R. Volkmar, Shawn Wood, Magdalena Laskawiec, Katherine Sansom, Herman van Engeland, Jane McGrath, Thomas H. Wassink, Su H. Chu, Elena Bacchelli, Carolyn Noakes, Ann Le Couteur, Catarina Correia, Ohsuke Migita, Bernie Devlin, Hilary Coon, Gillian Baird, Joseph Piven, Tom Berney, Ana Tryfon, Abdul Noor, Patrick Bolton, Latha Soorya, Vera Stoppioni, Stephen J. Guter, Joseph T. Glessner, Michael Gill, Christopher J. McDougle, Anthony J. Bailey, Margaret A. Pericak-Vance, Joachim Hallmayer, Christine M. Freitag, Penny Farrar, Kirsty Wing, Katherine E. Tansey, Bernadette Rogé, Michael Rutter, Christina Strawbridge, Brett S. Abrahams, Kerstin Wittemeyer, Laura J. Bierut, Tara Paton, Emily L. Crawford, Jonathan L. Haines, Alexander Kolevzon, Gillian Hughes, Lili Senman, James S. Sutcliffe, John B. Gilbert, Katerina Papanikolaou, Andrew R. Carson, Lynne E Cochrane, Regina Regan, Judith Miller, Susanne Thomson, Helen McConachie, Daisuke Sato, Richard Delorme, Jiannis Ragoussis, Eric Fombonne, Clara Lajonchere, Judith Conroy, Dalila Pinto, Aparna Prasad, Naisha Shah, Stanley F. Nelson, Sabine M. Klauck, Catalina Betancur, John B. Vincent, Eftichia Duketis, Jennifer L. Howe, Edwin H. Cook, Xiao-Qing Liu, Catherine Lord, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Department of Neurology, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry, University of Oxford [Oxford]-Warneford Hospital, Newcomen Centre, Guy's Hospital [London], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Child and Adolescent Mental Health, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Department of Child and Adolescent Psychiatry, Institute of psychiatry, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Autism Research Unit, University of Toronto-The Hospital for sick children [Toronto] (SickKids), Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Scientific Affairs, Autism Speaks, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], Disciplines of Genetics and Medicine, Memorial University of Newfoundland [St. John's], John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), University of Gothenburg (GU), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario], Manchester Academic Health Sciences Centre, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Department of Medicine, Autism Genetic Resource Exchange, Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nathan Kline Institute for Psychiatric Research (NKI), Nathan Kline Institute for Psychiatric Research, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-NYU Child Study Center, Centre d'Etudes et de Recherches en PsychoPathologie, Université Toulouse - Jean Jaurès (UT2J), Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Departments of Psychiatry and Neurology, Department of Psychiatry and Behavioral Sciences, Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), Centre for Addiction and Mental Health, Clarke Institute, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Institutes of Neuroscience and Health and Society, Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Carolina Institute for Developmental Disabilities, Social, Genetic and Developmental Psychiatry Centre, Washington University in Saint Louis (WUSTL), Howard Hughes Medical-Institute Carver College of Medicine-University of Iowa [Iowa City], Neuropsichiatria Infantile, Ospedale Santa Croce, Child Study Centre, Yale University School of Medicine, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], University of Alberta, Physiopathologie des Maladies du Système Nerveux Central, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Departments of Biostatistics and Medicine, This research was primarily supported by Autism Speaks (USA), the Health Research Board (HRB, Ireland), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute, and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health [HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH057881, MH061009, MH06359, MH066673, MH077930, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261], the Canadian Institutes for Health Research (CIHR), Assistance Publique-Hôpitaux de Paris (France), Autistica, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (grant: Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundação Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Médicale (France), Fundação para a Ciência e Tecnologia (Portugal), GlaxoSmithKline-CIHR Pathfinder Chair (Canada), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health [convention 181 of 19.10.2001], the John P Hussman Foundation (USA), McLaughlin Centre (Canada), Netherlands Organization for Scientific Research [Rubicon 825.06.031], Ontario Ministry of Research and Innovation (Canada), Royal Netherlands Academy of Arts and Sciences [TMF/DA/5801], the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award [075491/Z/04 UK]. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422)., University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, University of Oxford-Warneford Hospital, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Université de Toulouse (UT)-Université de Toulouse (UT), University of Pennsylvania, Betancur, Catalina, 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 Jr, 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.
Subjects: Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Genotype, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Databases, Genetic, Copy-number variation, MESH: Genetic Variation, Genetics (clinical), MESH: Databases, Genetic, Genetics, 0303 health sciences, education.field_of_study, MESH: Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH: European Continental Ancestry Group, Autism spectrum disorders, MESH: DNA Copy Number Variations, Genotyping, DNA Copy Number Variations, Genotype, Population, MESH: Autistic Disorder, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Genetic variation, Humans, Genetic Predisposition to Disease, ddc:610, Allele, Autistic Disorder, SNP association, education, Molecular Biology, Alleles, MESH: Genome, Human, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Genome, Human, MESH: Alleles, Haplotype, Genetic Variation, Genetic architecture, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: Genome-Wide Association Study, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: 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. Author has checked copyright TS 14.06.13 The subscript characters from the abstract have not copied across properly. TS
Published: 2010
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42. A genome-wide linkage and association scan reveals novel loci for autism

Author: Zak Kohane, Jeremy Goldberg, Carine Mantoulan, Shaun Purcell, Jessica Brian, Magdalena Laskawiec, Christopher A. Walsh, Irma Moilanen, Ridha Joober, Peter Szatmari, Olena Korvatska, Kerim Munir, James F. Gusella, Rudolph E. Tanzi, David L. Pauls, Generoso G. Gascon, Christine Stevens, Linda Lotspeich, John I. Nurnberger, Ramzi Nazir, Jonathan Green, Brian L. Yaspan, Marion Leboyer, Ann P. Thompson, Shun-Chiao Chang, Carolyn Bridgemohan, Louise Gallagher, Jeff Munson, Michael Gill, Guiqing Cai, Fritz Poustka, Regina Regan, Aislyn Cangialose, Gerard D. Schellenberg, Christopher J. McDougle, Christina Corsello, Wendy Roberts, Thomas H. Wassink, Majid Ghadami, Ellen M. Hanson, Benjamin M. Neale, Stacey Gabriel, Lonnie Zwaigenbaum, John Tsiantis, Hanna Ebeling, Sabine M. Klauck, Elaine LeClair, Bernie Devlin, Steven A. McCarroll, Ashley O'Connor, Andrew Pickles, Emily L. Crawford, Katja Jussila, Helen McConachie, Christopher Gillberg, Brenda E. Barry, Lou Kunkel, Seung Yun Yoo, Jennifer N. Partlow, Stephanie Brewster O'Neil, Ingrid A. Holm, Judith Miller, Guy A. Rouleau, Val C. Sheffield, Catherine Lord, Judith S. Palfrey, Ellen M. Wijsman, Astrid M. Vicente, Azam Hosseinipour, Ronald E. Becker, James S. Sutcliffe, Fred R. Volkmar, Marja Leena Mattila, Katerina Papanikolaou, Jennifer Reichert, Edwin H. Cook, Pamela Sklar, Elena Maestrini, Hilary Coon, Sek Won Kong, Stephen A. Haddad, Todd Green, Gillian Baird, Andrew Kirby, Patrick Bolton, Robert Sean Hill, Eric M. Morrow, Tom Berney, Jonathan L. Haines, Maryam Valujerdi, Casey Gates, David J. Posey, Karola Rehnström, Alistair T. Pagnamenta, Christine M. Freitag, Eric Fombonne, Janice Ware, Christian R. Marshall, Janine A. Lamb, Lauren A. Weiss, Agatino Battaglia, Nancy J. Minshew, Roksana Sasanfar, Elizabeth Baroni, Maretha de Jonge, Lennart von Wendt, Gina Hilton, Dalila Pinto, Nahit Motavalli Mukaddes, Ala Tolouei, Catalina Betancur, Michael Rutter, Tram Tran, Eftichia Duketis, Laurent Mottron, Margaret A. Pericak-Vance, Kristen West, Joachim Hallmayer, Kirsty Wing, Kerstin Wittemeyer, Rachel J. Hundley, Herman van Engeland, Judith Conroy, Mark J. Daly, Asif Hashmi, Michael L. Cuccaro, Geraldine Dawson, Sanna Kuusikko, Richard Anney, Anthony P. Monaco, Brian Winkloski, Samira Al-Saad, Dan E. Arking, Veronica J. Vieland, Stephen W. Scherer, Soher Balkhy, Kara Andresen, Rebecca L. Tomlinson, Joseph D. Buxbaum, Aravinda Chakravarti, Xiao-Qing Liu, Lindsay Jackson, Jaakko Ignatius, Catarina Correia, Leonard Rappaport, Heather Peters, Julie Gauthier, John R. Gilbert, Jeremy R. Parr, Carrie Sougnez, Katherine E. Tansey, Bennett L. Leventha, Annemarie Poustka, Daniel H. Geschwind, Annette Estes, Leena Peltonen, Maryam Rostami, Jeff Salt, David Altshuler, Simon Wallace, Susan E. Bryson, William M. Mahoney, Katy Renshaw, Robert M. Joseph, Lisa H. Albers, Inês Cabrito, Sean Ennis, Vanessa Hus, Guiomar Oliveira, Ann Le Couteur, Joseph Piven, Sandra L. Friedman, Penny Farrar, Joshua M. Korn, Sven Bölte, Camille W. Brune, Esau Simmons, Susan L. Santangelo, Andrew D. Paterson, Rita M. Cantor, Andrew B. West, Finny G Kuruvilla, Tiago R. Magalhaes, Andrew Green, Alison Schonwald, Stephen J. Guter, Anthony J. Bailey, Bernadette Rogé, William M. McMahon, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Johns Hopkins University (JHU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Betancur, Catalina, University of Helsinki, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), WEISS LA, ARKING DE, and GENE DISCOVERY PROJECT OF JOHNS HOPKINS & THE AUTISM CONSORTIUM, DALY MJ, CHAKRAVARTI A, BRUNE CW, WEST K, O'CONNOR A, HILTON G, TOMLINSON RL, WEST AB, COOK EH JR, CHAKRAVARTI A, WEISS LA, GREEN T, CHANG SC, GABRIEL S, GATES C, HANSON EM, KIRBY A, KORN J, KURUVILLA F, MCCARROLL S, MORROW EM, NEALE B, PURCELL S, SASANFAR R, SOUGNEZ C, STEVENS C, ALTSHULER D, GUSELLA J, SANTANGELO SL, SKLAR P, TANZI R, DALY MJ, ANNEY R, BAILEY AJ, BAIRD G, BATTAGLIA A, BERNEY T, BETANCUR C, BÖLTE S, BOLTON PF, BRIAN J, BRYSON SE, BUXBAUM JD, CABRITO I, CAI G, CANTOR RM, COOK EH JR, COON H, CONROY J, CORREIA C, CORSELLO C, CRAWFORD EL, CUCCARO ML, DAWSON G, DE JONGE M, DEVLIN B, DUKETIS E, ENNIS S, ESTES A, FARRAR P, FOMBONNE E, FREITAG CM, GALLAGHER L, GESCHWIND DH, GILBERT J, GILL M, GILLBERG C, GOLDBERG J, GREEN A, GREEN J, GUTER SJ, HAINES JL, HALLMAYER JF, HUS V, KLAUCK SM, KORVATSKA O, LAMB JA, LASKAWIEC M, LEBOYER M, COUTEUR AL, LEVENTHAL BL, LIU XQ, LORD C, LOTSPEICH LJ, MAESTRINI E, MAGALHAES T, MAHONEY W, MANTOULAN C, MCCONACHIE H, MCDOUGLE CJ, MCMAHON WM, MARSHALL CR, MILLER J, MINSHEW NJ, MONACO AP, MUNSON J, NURNBERGER JI JR, OLIVEIRA G, PAGNAMENTA A, PAPANIKOLAOU K, PARR JR, PATERSON AD, PERICAK-VANCE MA, PICKLES A, PINTO D, PIVEN J, POSEY DJ, POUSTKA A, POUSTKA F, REGAN R, REICHERT J, RENSHAW K, ROBERTS W, ROGE B, RUTTER ML, SALT J, SCHELLENBERG GD, SCHERER SW, SHEFFIELD V, SUTCLIFFE JS, SZATMARI P, TANSEY K, THOMPSON AP, TSIANTIS J, VAN ENGELAND H, VICENTE AM, VIELAND VJ, VOLKMAR F, WALLACE S, WASSINK TH, WIJSMAN EM, WING K, WITTEMEYER K, YASPAN BL, ZWAIGENBAUM L, MORROW EM, YOO SY, HILL RS, MUKADDES NM, BALKHY S, GASCON G, AL-SAAD S, HASHMI A, WARE J, JOSEPH RM, LECLAIR E, PARTLOW JN, BARRY B, WALSH CA, PAULS D, MOILANEN I, EBELING H, MATTILA ML, KUUSIKKO S, JUSSILA K, IGNATIUS J, SASANFAR R, TOLOUEI A, GHADAMI M, ROSTAMI M, HOSSEINIPOUR A, VALUJERDI M, SANTANGELO SL, ANDRESEN K, WINKLOSKI B, HADDAD S, KUNKEL L, KOHANE Z, TRAN T, KONG SW, O'NEIL SB, HANSON EM, HUNDLEY R, HOLM I, PETERS H, BARONI E, CANGIALOSE A, JACKSON L, ALBERS L, BECKER R, BRIDGEMOHAN C, FRIEDMAN S, MUNIR K, NAZIR R, PALFREY J, SCHONWALD A, SIMMONS E, RAPPAPORT LA, GAUTHIER J, MOTTRON L, JOOBER R, FOMBONNE E, ROULEAU G, REHNSTROM K, VON WENDT L, PELTONEN L.
Subjects: Perturbação Autística, Internationality, Genetic Linkage, Genome-wide association study, MESH: Semaphorins, Semaphorins, [SDV.GEN] Life Sciences [q-bio]/Genetics, 0302 clinical medicine, Neurodevelopmental disorder, Heritability of autism, MESH: Nerve Tissue Proteins, Association mapping, Genetics, 0303 health sciences, Multidisciplinary, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Brain, Chromosome Mapping, Chromosomes, Human, Pair 5, MESH: Membrane Proteins, MESH: Chromosomes, Human, Pair 5, MESH: Autistic Disorder, MESH: Genetic Linkage, Single-nucleotide polymorphism, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, MESH: Brain, Genetic linkage, medicine, Humans, Genetic Predisposition to Disease, Autistic Disorder, MESH: Sample Size, 030304 developmental biology, Genetic association, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Membrane Proteins, medicine.disease, Sample Size, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: Genome-Wide Association Study, MESH: Internationality, Autism, MESH: Chromosome Mapping, Predisposição Genética para Doença, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Member of the Autism Genome Project Consortium: Astrid M. Vicente Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
Published: 2009
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43. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Author: Peter, Szatmari, Andrew D, Paterson, Lonnie, Zwaigenbaum, Wendy, Roberts, Jessica, Brian, Xiao-Qing, Liu, John B, Vincent, Jennifer L, Skaug, Ann P, Thompson, Lili, Senman, Lars, Feuk, Cheng, Qian, Susan E, Bryson, Marshall B, Jones, Christian R, Marshall, Stephen W, Scherer, Veronica J, Vieland, Christopher, Bartlett, La Vonne, Mangin, Rhinda, Goedken, Alberto, Segre, Margaret A, Pericak-Vance, Michael L, Cuccaro, John R, Gilbert, Harry H, Wright, Ruth K, Abramson, Catalina, Betancur, Thomas, Bourgeron, Christopher, Gillberg, Marion, Leboyer, Joseph D, Buxbaum, Kenneth L, Davis, Eric, Hollander, Jeremy M, Silverman, Joachim, Hallmayer, Linda, Lotspeich, James S, Sutcliffe, Jonathan L, Haines, Susan E, Folstein, Joseph, Piven, Thomas H, Wassink, Val, Sheffield, Daniel H, Geschwind, Maja, Bucan, W Ted, Brown, Rita M, Cantor, John N, Constantino, T Conrad, Gilliam, Martha, Herbert, Clara, Lajonchere, David H, Ledbetter, Christa, Lese-Martin, Janet, Miller, Stan, Nelson, Carol A, Samango-Sprouse, Sarah, Spence, Matthew, State, Rudolph E, Tanzi, Hilary, Coon, Geraldine, Dawson, Bernie, Devlin, Annette, Estes, Pamela, Flodman, Lambertus, Klei, William M, McMahon, Nancy, Minshew, Jeff, Munson, Elena, Korvatska, Patricia M, Rodier, Gerard D, Schellenberg, Moyra, Smith, M Anne, Spence, Chris, Stodgell, Ping Guo, Tepper, Ellen M, Wijsman, Chang-En, Yu, Bernadette, Rogé, Carine, Mantoulan, Kerstin, Wittemeyer, Annemarie, Poustka, Bärbel, Felder, Sabine M, Klauck, Claudia, Schuster, Fritz, Poustka, Sven, Bölte, Sabine, Feineis-Matthews, Evelyn, Herbrecht, Gabi, Schmötzer, John, Tsiantis, Katerina, Papanikolaou, Elena, Maestrini, Elena, Bacchelli, Francesca, Blasi, Simona, Carone, Claudio, Toma, Herman, Van Engeland, Maretha, de Jonge, Chantal, Kemner, Frederieke, Koop, Frederike, Koop, Marjolein, Langemeijer, Marjolijn, Langemeijer, Channa, Hijmans, Channa, Hijimans, Wouter G, Staal, Gillian, Baird, Patrick F, Bolton, Michael L, Rutter, Emma, Weisblatt, Jonathan, Green, Catherine, Aldred, Julie-Anne, Wilkinson, Andrew, Pickles, Ann, Le Couteur, Tom, Berney, Helen, McConachie, Anthony J, Bailey, Kostas, Francis, Gemma, Honeyman, Aislinn, Hutchinson, Jeremy R, Parr, Simon, Wallace, Anthony P, Monaco, Gabrielle, Barnby, Kazuhiro, Kobayashi, Janine A, Lamb, Ines, Sousa, Nuala, Sykes, Edwin H, Cook, Stephen J, Guter, Bennett L, Leventhal, Jeff, Salt, Catherine, Lord, Christina, Corsello, Vanessa, Hus, Daniel E, Weeks, Fred, Volkmar, Maïté, Tauber, Eric, Fombonne, Andy, Shih, Kacie J, Meyer, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Centre for Applied Genomics, Toronto, University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Department of Pediatrics, University of Alberta, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Department of Psychiatry, University of Toronto, Departments of Pediatrics and Psychology, Dalhousie University [Halifax], Department of Neural and Behavioral Sciences, Pennsylvania State University (Penn State), Penn State System-Penn State System, Department of Molecular Genetics [Toronto], Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Department of Pathology and Laboratory Medicine, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Computer Science, University of Iowa [Iowa City], John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], W.S. Hall Psychiatric Institute, University of South Carolina [Columbia], Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Institute of Child Health, University College of London [London] (UCL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Neuroscience, PennState Meteorology Department, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Psychiatry and Behavioral Sciences [Stanford], Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Johns Hopkins University (JHU), Carolina Institute for Developmental Disabilities, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], University of Iowa [Iowa City]-Howard Hughes Medical-Institute Carver College of Medicine, Department of Neurology, UCLA School of Medicine, Department of Genetics, University of Pennsylvania [Philadelphia]-School of Medicine, N.Y.S. Institute for Basic Research in Developmental Disabilities, Department of Human Genetics, UCLA, University of California [Los Angeles] (UCLA), University of California-University of California-Semel Institute, Washington University in Saint Louis (WUSTL), University of Chicago, Harvard Medical School [Boston] (HMS), Autism Genetic Resource Exchange, Autism Speaks, Emory University [Atlanta, GA], Developmental Brain and Behaviour Unit, University of Southampton, Cure Autism Now, Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Children's National Medical Center, The George Washington University (GW), Massachusetts General Hospital, Massachusetts General Hospital [Boston], Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Autism Speaks and the Department of Psychiatry, Department of Speech and Hearing Sciences [Washington], University of Washington [Seattle], University of California [Irvine] (UCI), University of California-University of California, Department of Psychiatry and Behavioral Sciences, Department of OB/GYN, University of Rochester Medical Center, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Department of Epidemiology, University of Pittsburgh (PITT), Departments of Biostatistics and Medicine, Department of Medicine, Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Centre de Référence du Syndrome de Prader-Willi, CHU Toulouse [Toulouse], University of Oxford [Oxford]-Warneford Hospital, Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, University Department of Child Psychiatry, National and Kapodistrian University of Athens (NKUA), Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Medical Genetics Laboratory, Policlinico S. Orsola-Malpighi, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Department of Neurocognition, Maastricht University [Maastricht], Newcomen Centre, Guy's Hospital [London], Department of Child and Adolescent Psychiatry, Institute of psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, University of Cambridge Clinical School, University of Cambridge [UK] (CAM), Manchester Academic Health Sciences Centre, Department of Medicine, Manchester, University of Manchester [Manchester]-School of Epidemiology and Health Science, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), Child and Adolescent Mental Health, Newcastle University [Newcastle], Institutes of Neuroscience and Health and Society, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Centre for Integrated Genomic Medical Research, Manchester, University of Manchester [Manchester], Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Institute for Juvenile Research, University of Illinois [Chicago] (UIC), Department of Disability and Human Development, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Human Genetics Department, SFU Discrete Mathematics Group (SFU-DMG), Simon Fraser University (SFU.ca), Child Study Centre, Yale University School of Medicine, Centre d'Endocrinologie, Maladies Osseuses, Génétique et Gynécologie Médicale, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), Scientific Affairs, Autism Genome Project Consortium, RS: FPN CN II, Cognitive Neuroscience, MUMC+: HZC Klinische Neurofysiologie (5), The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, University of California (UC)-University of California (UC)-Semel Institute, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), King‘s College London-The Institute of Psychiatry, Yale School of Medicine [New Haven, Connecticut] (YSM), Betancur, Catalina, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-School of Medicine, University of Pennsylvania, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Oxford-Warneford Hospital, University of Oxford, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT), Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, Vincent JB, Skaug JL, Thompson AP, Senman L, Feuk L, Qian C, Bryson SE, Jones MB, Marshall CR, Scherer SW, Vieland VJ, Bartlett C, Mangin LV, Goedken R, Segre A, Pericak-Vance MA, Cuccaro ML, Gilbert JR, Wright HH, Abramson RK, Betancur C, Bourgeron T, Gillberg C, Leboyer M, Buxbaum JD, Davis KL, Hollander E, Silverman JM, Hallmayer J, Lotspeich L, Sutcliffe JS, Haines JL, Folstein SE, Piven J, Wassink TH, Sheffield V, Geschwind DH, Bucan M, Brown WT, Cantor RM, Constantino JN, Gilliam TC, Herbert M, Lajonchere C, Ledbetter DH, Lese-Martin C, Miller J, Nelson S, Samango-Sprouse CA, Spence S, State M, Tanzi RE, Coon H, Dawson G, Devlin B, Estes A, Flodman P, Klei L, McMahon WM, Minshew N, Munson J, Korvatska E, Rodier PM, Schellenberg GD, Smith M, Spence MA, Stodgell C, Tepper PG, Wijsman EM, Yu CE, Roge B, Mantoulan C, Wittemeyer K, Poustka A, Felder B, Klauck SM, Schuster C, Poustka F, Bolte S, Feineis-Matthews S, Herbrecht E, Schmotzer G, Tsiantis J, Papanikolaou K, Maestrini E, Bacchelli E, Blasi F, Carone S, Toma C, Van Engeland H, de Jonge M, Kemner C, Koop F, Langemeijer M, Hijimans C, Staal WG, Baird G, Bolton PF, Rutter ML, Weisblatt E, Green J, Aldred C, Wilkinson JA, Pickles A, Le Couteur A, Berney T, McConachie H, Bailey AJ, Francis K, Honeyman G, Hutchinson A, Parr JR, Wallace S, Monaco AP, Barnby G, Kobayashi K, Lamb JA, Sousa I, Sykes N, Cook EH, Guter SJ, Leventhal BL, Salt J, Lord C, Corsello C, Hus V, Weeks DE, Volkmar F, Tauber M, Fombonne E, and Shih A.
Subjects: Male, genetic structures, Genetic Linkage, Neurexin, [SDV.GEN] Life Sciences [q-bio]/Genetics, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Heritability of autism, Copy-number variation, MESH: Genetic Variation, Genetics, 0303 health sciences, medicine.diagnostic_test, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, Chromosome Mapping, 3. Good health, Female, MESH: Genetic Linkage, MESH: Autistic Disorder, Epigenetics of autism, Biology, Article, 03 medical and health sciences, Genetic linkage, mental disorders, medicine, Humans, MESH: Chromosome Aberrations, Family, Genetic Predisposition to Disease, Genetic Testing, Autistic Disorder, MESH: Family, 030304 developmental biology, Genetic testing, Chromosome Aberrations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Genetic Variation, medicine.disease, Genetic architecture, MESH: Male, MESH: Lod Score, Autism, Lod Score, MESH: Chromosome Mapping, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
Published: 2007
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44. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Author: Veronica J. Vieland, Stephen W. Scherer, Alison K. Merikangas, Naisha Shah, Edwin H. Cook, William M. McMahon, Kirsty Wing, Sabata C. Lund, Jacob A. S. Vorstman, Judith Conroy, Sabine M. Klauck, John B. Vincent, Astrid M. Vicente, Carine Mantoulan, Barbara Parrini, Jeremy R. Parr, Herman van Engeland, Jane McGrath, Guiomar Oliveira, Jonathan Green, James S. Sutcliffe, Peter Szatmari, Ann Le Couteur, Katerina Papanikolaou, Joseph Piven, Andrew Pickles, Gillian Baird, Inês Sousa, Gerard D. Schellenberg, Catarina Correia, Bennett L. Leventhal, Helen McConachie, Joseph T. Glessner, Fritz Poustka, Alistair T. Pagnamenta, Marion Leboyer, Nuala Sykes, Elena Maestrini, Penny Farrar, Maïté Tauber, Suzanne Foley, Richard Holt, Lonnie Zwaigenbaum, David J. Posey, John Tsiantis, Alexander Kolevzon, Agatino Battaglia, Maretha de Jonge, Hilary Coon, Gillian Hughes, John R. Gilbert, Patrick Bolton, Louise Gallagher, Jeff Munson, Kathy White, Michael L. Cuccaro, Annemarie Poustka, Daniel H. Geschwind, Richard Delorme, Annette Estes, Christine M. Freitag, Jillian P. Casey, Joana Almeida, Dalila Pinto, Simon Wallace, Sean Brennan, Stephen J. Guter, Stanley F. Nelson, Michael Rutter, Ghazala Mirza, Anthony J. Bailey, Christina Corsello, Kerstin Wittemeyer, Christian R. Marshall, Janine A. Lamb, Catherine Lord, Hakon Hakonarson, Jiannis Ragoussis, Catalina Betancur, Geraldine Dawson, Eftichia Duketis, Sean Ennis, Fiorella Minopoli, Christopher Gillberg, Vera Stoppioni, Bridget A. Fernandez, Frederico Duque, Eric Fombonne, Ellen M. Wijsman, Bernadette Rogé, Vanessa Hus, Susan E. Folstein, Jonathan L. Haines, Denis C. Shields, Tiago R. Magalhaes, Andrew Green, Thomas Bourgeron, Brian L. Yaspan, Ann P. Thompson, Gudrun Nygren, Judith Miller, Susanne Thomson, Roberta Igliozzi, Ana Filipa Sequeira, Kai Wang, Brett S. Abrahams, John I. Nurnberger, Michael Gill, Thomas H. Wassink, Christopher J. McDougle, Marc N. Coutanche, Anthony P. Monaco, Nadia Bolshakova, Cecilia Kim, Raffaella Tancredi, Rita M. Cantor, Phil Cali, Fred R. Volkmar, Tom Berney, Margaret A. Pericak-Vance, Joachim Hallmayer, Joseph D. Buxbaum, Elena Bacchelli, Latha Soorya, Richard Anney, Regina Regan, University of Bologna, Open University of Israël, IRCCS Fondazione Stella Maris [Pisa], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Goethe-University Frankfurt am Main, Memorial University of Newfoundland [St. John's], McGill University = Université McGill [Montréal, Canada], Johns Hopkins University (JHU), Autism Research Centre and Section of Developmental Psychiatry, University of Cambridge [UK] (CAM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Psychiatrie génétique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mondor de Recherche Biomédicale, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Australian Resources Research Centre, Kensington, Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital des Enfants, CHU Toulouse [Toulouse], School of Chemistry, Dalhousie University [Halifax], DLR Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), Department of Human Genetics, University of Chicago, University of Alberta, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), University of Koblenz-Landau, McMaster University [Hamilton, Ontario], The authors acknowledge the families participating in the study and the main funders of the Autism Genome Project Consortium (AGP): Autism Speaks (USA), the Health Research Board (HRB, Ireland), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute, and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health (NIH grants HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH57881, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261), the Canadian Institute for Advanced Research (CIFAR), the Canadian Institutes for Health Research (CIHR), Assistance Publique–Hôpitaux de Paris (France), Autistica, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (grant Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundação Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Médicale (France), Fundação para a Ciência e Tecnologia (Portugal), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health (convention 181 of 19.10.2001), the John P. Hussman Foundation (USA), McLaughlin Centre (Canada), Ontario Ministry of Research and Innovation (Canada), the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award 075491/Z/04 (UK). We acknowledge support from the Autism Genetic Resource Exchange (AGRE) and Autism Speaks. We gratefully acknowledge the resources provided by the AGRE consortium and the participating AGRE families. AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). We wish to acknowledge the National Children’s Research Centre Our Lady’s Children’s Hospital Crumlin Ireland for providing additional support and the Wellcome Trust Case–Control Consortium for providing data sets that were used as part of this study. J.P.C is supported by an EMBARK postgraduate award from the Irish Research Council for Science, Engineering and Technology (IRCSET)., The AGRE Consortium, Casey JP, Magalhaes T, Conroy JM, Regan R, Shah N, Anney R, Shields DC, Abrahams BS, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolton PF, 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 BA, Folstein SE, Foley S, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Green J, Guter SJ, Hakonarson H, Holt R, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Lamb JA, Leboyer M, Le Couteur A, Leventhal BL, Lord C, Lund SC, Maestrini E, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Miller J, Minopoli F, Mirza GK, Munson J, Nelson SF, Nygren G, Oliveira G, Pagnamenta AT, Papanikolaou K, Parr JR, Parrini B, Pickles A, Pinto D, Piven J, Posey DJ, Poustka A, Poustka F, Ragoussis J, Roge B, Rutter ML, Sequeira AF, Soorya L, Sousa I, Sykes N, Stoppioni V, Tancredi R, Tauber M, Thompson AP, Thomson S, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman JA, Wallace S, Wang K, Wassink TH, White K, Wing K, Wittemeyer K, Yaspan BL, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Geschwind DH, Haines JL, Hallmayer J, Monaco AP, Nurnberger JI Jr, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vieland VJ, Wijsman EM, Green A, Gill M, Gallagher L, Vicente A, Ennis S., McGill University, Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Bologna/Università di Bologna, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Candidate gene, Genome-wide association study, Linkage Disequilibrium, MESH: Child Development Disorders, Pervasive, Cohort Studies, MESH: Genotype, 0302 clinical medicine, MESH: Child, Cluster Analysis, Genetics(clinical), Copy-number variation, Child, MESH: Cohort Studies, Genetics (clinical), Original Investigation, SNPS, Genetics, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Nuclear Family, MESH: Polymorphism, Single Nucleotide, Homozygote, MESH: Genetic Predisposition to Disease, Middle Aged, Autism spectrum disorder (ASD), 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: DNA Copy Number Variations, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Homozygote, Adult, DNA Copy Number Variations, Genotype, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Nuclear Family, 03 medical and health sciences, HOMOZYGOSITY MAPPING, mental disorders, medicine, Humans, Genetic Predisposition to Disease, ddc:610, AUTISM, GENOME-WIDE ASSOCIATION, education, 030304 developmental biology, MESH: Humans, Genetic heterogeneity, Haplotype, MESH: Adult, MESH: Haplotypes, medicine.disease, MESH: Cluster Analysis, MESH: Male, Haplotypes, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: Genome-Wide Association Study, Autism, MESH: Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: 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. Electronic supplementary material The online version of this article (doi:10.1007/s00439-011-1094-6) contains supplementary material, which is available to authorized users.
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45. Health checks for autistic adults: study protocol for a cluster randomised controlled trial.

Author: Parr JR, Taylor H, Wilson C, Scarlett C, Al-Asmori S, Buckley C, Cooper SA, Fernandez-Garcia C, Finch T, Lees R, Lennox N, Merrick H, Moss S, Nicolaidis C, Osbourne M, Raymaker DM, Robinson T, Urbanowicz A, Wason JMS, and Ingham B
Subjects: Adult, Humans, Cost-Benefit Analysis, Health Care Costs, Quality of Life, Quality-Adjusted Life Years, Randomized Controlled Trials as Topic, Time Factors, Autistic Disorder diagnosis, Autistic Disorder economics, Primary Health Care economics
Abstract: Background: Autistic people commonly have physical and mental health conditions. They also frequently experience barriers to accessing healthcare, contributing to problems identifying and treating health conditions. These factors may lead to increased and earlier morbidity and lower average life expectancy for autistic people. Health checks specifically designed for autistic people, incorporating adjustments to healthcare, may help to overcome these barriers and reduce health inequalities. This trial aims to investigate the clinical and cost-effectiveness of a primary care health check for autistic adults and explore factors related to implementation such as acceptability and feasibility of delivery. The trial is co-designed and delivered by health professionals, autistic people, carers and supporters, and researchers., Methods: This is a clinical and cost-effectiveness, cluster randomised controlled trial of a primary care health check for autistic adults. Primary care practices will be randomised into one of two groups (intervention or control). Two hundred autistic adults (aged 18 years and over) who provide baseline data will be recruited via participating practices. Data will be collected through quantitative and qualitative methods. The primary outcome will be the incidence of new health needs/conditions detected and met at 9 months (data gathered from participant's GP records). Secondary outcomes will include the following: cost-effectiveness, measured as incremental cost per quality-adjusted life year gained over 9 months; the extent of health monitoring and health promotion needs met at 9 months; the incidence of social care needs identified at 9 months; changes in participant or carer general health; changes in quality of life; primary and secondary health and social care resource usage and costs. A qualitative study will explore views about the acceptability of the health check, its utility and future use., Discussion: This study will examine the effectiveness and cost-effectiveness of a primary care health check for autistic adults in identifying new health conditions and needs. If the intervention is effective, it would provide strong evidence for implementation into routine healthcare, therefore enabling earlier health condition diagnosis and opportunities for treatment, reducing the health inequalities experienced by autistic people., Trial Registration: ISRCTN, retrospectively registered on 20 July 2023. https://www.isrctn.com/ISRCTN30156776 (ISRCTN registration number: 30156776)., Competing Interests: Declarations. Ethics approval and consent to participate: This study received ethical approval from the North Wales Research Ethics Committee (Wales REC 5) and the NHS Health Research Authority (ref: 21/WA/0196; IRAS Project ID: 272808). Informed consent will be obtained from all study participants. Important protocol modifications will be reported in writing to relevant parties. A list of all protocol modifications will be provided during study reporting. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. Primary care practices are receiving funding for research activities at sites. To the best of our knowledge, primary care sites have no competing or financial interests., (© 2024. The Author(s).)
Published: 2024
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46. Parent carer and disabled young people's perspectives on the impacts of changes to service provision for children and young people in England during the COVID-19 pandemic: a qualitative study.

Author: Merrick H, Driver H, Potts L, Exley C, Allard A, Morris C, Parr JR, and Pennington L
Subjects: Humans, Child, Adolescent, Male, Female, England epidemiology, Child, Preschool, Children with Disabilities, Adult, Health Services Accessibility, Child Health Services organization & administration, Young Adult, Pandemics, Telemedicine, COVID-19 epidemiology, Qualitative Research, Parents psychology, SARS-CoV-2, Caregivers psychology
Abstract: Objectives: In England, the delivery of health, education and social care services changed substantially during COVID-19. Some services closed, some had reduced capacity and there was a shift to the use of telehealth. This study aimed to understand how families of children and young people with neurodisability experienced these service changes, what did or did not work well for them and what impact the service changes had on them., Design: Qualitative study with parent carers of children (aged 0-19 years) with neurodisability accessing children's health, social care and education-based services during the COVID-19 pandemic., Setting: Participants were recruited from five local authority areas in England and interviewed via telephone and/or video call., Participants: 48 parent carers (45 mothers, three fathers) were interviewed and nine young people (aged 8-16 years). Across the parent carers there were 55 children with neurodisability (43 males, 12 females), ranging from 3 to 19 years. Children had a range of diagnoses, including autism, attention deficit hyperactivity disorder, cerebral palsy, genetic conditions and epilepsy. Nine young people (aged 8-16 years; eight males, one female) were interviewed; two individually, three in a focus group and four with their parent carer., Results: Four themes were identified: (1) communication of service changes, (2) access to services during the pandemic, (3) impacts of service changes and (4) learning for future emergencies and resetting services. Communication of service changes was reported as poor and confusing. Access to services during the pandemic varied. Medical services continued with least disruption; therapeutic, education-based and social care services were severely disrupted. Service changes had a detrimental impact on families coping with high levels of medical care and physical and behavioural support. Young people experienced negative impacts of service change on their physical, mental and behavioural health., Conclusions: Services for children with neurodisability require a person-led, family centred approach with strong multidisciplinary team working. Findings indicated the need for improved communication within and between services, and between services and families and young people. Planning for future emergencies needs to factor in the specific health and care needs of children with neurodisability and maintain access to services, in particular, those accessed through schools., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Published: 2024
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47. A Pilot Randomised Control Trial Exploring the Feasibility and Acceptability of Delivering a Personalised Modular Psychological Intervention for Anxiety Experienced by Autistic Adults: Personalised Anxiety Treatment-Autism (PAT-A).

Author: Rodgers J, Brice S, Welsh P, Ingham B, Wilson C, Evans G, Steele K, Cropper E, Le Couteur A, Freeston M, and Parr JR
Subjects: Humans, Male, Female, Adult, Pilot Projects, Single-Blind Method, Quality of Life psychology, Young Adult, Patient Acceptance of Health Care psychology, Middle Aged, Anxiety Disorders therapy, Anxiety Disorders psychology, Treatment Outcome, Psychosocial Intervention methods, Precision Medicine methods, Autistic Disorder therapy, Autistic Disorder psychology, Feasibility Studies, Anxiety therapy, Anxiety psychology
Abstract: Anxiety is commonly experienced by autistic people and impacts on quality of life and social participation. New anxiety interventions are required to effectively meet the needs of autistic people. Personalised Anxiety Treatment-Autism (PAT-A©) is a bespoke, modular approach to treating anxiety in up to 12 sessions. This study explored the feasibility and acceptability of delivering PAT-A© in the UK National Health Service (NHS). A single-blind randomised controlled trial design. Thirty-four autistic adults were recruited via clinical services and randomised to receive either PAT-A© or enhanced treatment as usual (CCSP). Outcome assessments relating to anxiety, quality of life and related constructs were completed at baseline, immediately post intervention; and at 3 and 12 months. Seventy-one percent of the PAT-A© group and 65% of the CCSP met diagnostic threshold for at least three anxiety disorders. Retention was good across both groups, with 82% (N = 14/17) completing the full course of PAT-A© and 71% (N = 12/17) attending both psychoeducational sessions in CCSP. 94% in PAT-A© and 82% in CCSP completed some follow up assessment 3 months post-intervention. Thematic analysis of interview data revealed that many participants valued the personalised approach, developed transferable skills and experienced positive changes to their anxiety. Participants were willing to be recruited and randomised, PAT-A© was feasible to deliver in the NHS and the trial methods and materials were acceptable. Our findings indicate that a fully powered clinical and cost-effectiveness trial of PAT-A© is warranted., (© 2023. The Author(s).)
Published: 2024
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48. Policy and practice recommendations for services for disabled children during emergencies: Learning from COVID-19.

Author: Merrick H, Morris C, Allard A, Parr JR, and Pennington L
Abstract: Aim: To seek consensus on recommendations for the delivery of services to disabled children in England during future emergencies., Method: Candidate recommendations were drafted based on our related mapping review and qualitative research related to experiences during the COVID-19 pandemic. Iterative workshops with professionals and parent carers helped to refine the recommendations. A Delphi survey, rating the importance of each recommendation, was conducted with (1) parent carers of disabled children, (2) disabled young people aged 8 to 19 years, and (3) health, education, and social care professionals. A consensus meeting was convened online to discuss the findings and ratify the recommendations., Results: Twenty-eight recommendations were included in the Delphi survey. There were 141 participants in round 1 and 91 in round 2. Seven recommendations reached the agreed consensus criteria for being critical across all stakeholder groups, while 21 recommendations did not reach consensus across all groups. Fourteen participants ratified 23 recommendations, which when aggregated and refined further produced our final 19 recommendations., Interpretation: Reductions in services for disabled children and their families during the COVID-19 pandemic had serious and lasting consequences. This study enabled parent carers, disabled young people, and health, education, and social care professionals to agree recommendations on services for disabled children during future emergencies., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)
Published: 2024
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49. Professional perspectives on facilitators and barriers for high quality provision of health, education and social care services to disabled children in England during the COVID-19 pandemic: a qualitative study.

Author: Merrick H, Driver H, Main C, Potts L, Russell S, Exley C, Allard A, Morris C, Parr JR, and Pennington L
Subjects: Humans, England epidemiology, Child, SARS-CoV-2, Male, Female, Pandemics, Child Health Services organization & administration, Child Health Services standards, Focus Groups, Interviews as Topic, Attitude of Health Personnel, Health Personnel psychology, COVID-19 epidemiology, Children with Disabilities, Qualitative Research, Social Work organization & administration
Abstract: Objectives: To understand how health, education and social care services for disabled children changed during the COVID-19 pandemic, what did or did not work well and what the impacts of service changes were on both professionals and families., Design: Qualitative study using semistructured interviews., Setting: Telephone and video call interviews and focus groups with professionals working in one of five local authority areas in England., Participants: 78 health, education and social care professionals working with children in one of five local authority areas in England., Results: There was a significant disruption to services and reduced contact with families during the early stages of the pandemic; nevertheless, professionals were able to reflect on innovative ways they interacted with and sought to support and maintain health, education and social care provision to disabled children and their families. As waitlists have substantially increased, this and the longevity of the pandemic were perceived to have had negative consequences for staff health and well-being, the health and psychosocial outcomes of children and young people, and their parent carers., Conclusions: Key learning from this study for service recovery and planning for future emergencies is the need to be able to identify disabled children, classify their level of need and risk, assess the impact of loss of services and maintain clear communication across services to meet the needs of disabled children. Finally, services need to work collaboratively with families to develop child-centred care to strengthen resilience during service disruption., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Published: 2024
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50. The development of pGALSplus: evaluating feasibility and acceptability of an assessment to facilitate the identification and triage of children with musculoskeletal presentations.

Author: Mercer V, Smith N, Guglieri M, Jones SA, Parr JR, Foster HE, and Jandial S
Abstract: Objectives: Healthcare professionals (HCPs) need to identify potentially serious musculoskeletal (MSK) presentations in children and refer them to specialists appropriately. Our aim was to develop 'pGALSplus' (paediatric gait, arms, legs and spine plus) to support clinical assessment, aid decision-making and assess feasibility and acceptability in exemplar MSK pathologies., Methods: We used a three-phase mixed methods approach: phase 1, preliminary stakeholder engagement and scoping review to propose pGALSplus; phase 2, iterative development of pGALSplus involving an expert working group; and phase 3, testing the feasibility of pGALSplus in exemplar MSK conditions [JIA, mucopolysaccharidoses (MPS), muscular dystrophy (MD), developmental coordination disorder (DCD) and healthy controls (HCs)]. The final pGALSplus was derived from analysis of phase 3 data and feedback from HCPs, families and expert consensus input from an international e-survey ( n = 22) and virtual event ( n = 13)., Results: Feasibility was tested in 45 children (JIA, n = 10; MPS, n = 6; MD, n = 9; DCD, n = 10; HCs, n = 10). Overall the assessment was achievable in the target age range (2-10 years) and quick to complete [median 12 min (range 8-20)], with high acceptability from families. Expert feedback deemed pGALSplus to be very useful and of particular use to non-specialists in MSK paediatrics. The final pGALSplus comprises 26 clinical observations/skills with a colour-coding approach to aid decision-making and identification of more serious MSK presentations and additional resources to support its use in clinical practice., Conclusions: pGALSplus is a novel evidence- and consensus-based assessment building on pGALS, with high acceptability and feasibility. As community-based MSK assessment in children becomes more established, we propose that pGALSplus will facilitate and inform decision-making to promote access to specialist care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Published: 2024
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