Standard
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. / Anney, Richard J.L.; Ripke, Stephan; Anttila, Verneri; Grove, Jakob; Holmans, Peter; Huang, Hailiang; Klei, Lambertus; Lee, Phil H.; Medland, Sarah E.; Neale, Benjamin; Robinson, Elise; Weiss, Lauren A.; Zwaigenbaum, Lonnie; Yu, Timothy W.; Wittemeyer, Kerstin; Willsey, A. Jeremy; Wijsman, Ellen M.; Werge, Thomas; Wassink, Thomas H.; Waltes, Regina; Walsh, Christopher A.; Wallace, Simon; Vorstman, Jacob A.S.; Vieland, Veronica J.; Vicente, Astrid M.; Vanengeland, Herman; Tsang, Kathryn; Thompson, Ann P.; Szatmari, Peter; Svantesson, Oscar; Steinberg, Stacy; Stefansson, Kari; Stefansson, Hreinn; State, Matthew W.; Soorya, Latha; Silagadze, Teimuraz; Scherer, Stephen W.; Schellenberg, Gerard D.; Sandin, Sven; Sanders, Stephan J.; Saemundsen, Evald; Rouleau, Guy A.; Rogé, Bernadette; Roeder, Kathryn; Roberts, Wendy; Reichert, Jennifer; Reichenberg, Abraham; Rehnström, Karola; Regan, Regina; Poustka, Fritz; Poultney, Christopher S.; Piven, Joseph; Pinto, Dalila; Pericak-Vance, Margaret A.; Pejovic-Milovancevic, Milica; Pedersen, Marianne Giørtz; Pedersen, Carsten Bøcker; Paterson, Andrew D.; Parr, Jeremy R.; Pagnamenta, Alistair T.; Oliveira, Guiomar; Nurnberger, John I.; Nordentoft, Merete; Murtha, Michael T.; Mouga, Susana; Mortensen, Preben Bo; Mors, Ole; Morrow, Eric M.; Moreno-De-Luca, Daniel; Monaco, Anthony P.; Minshew, Nancy; Merikangas, Alison; McMahon, William M.; McGrew, Susan G.; Mattheisen, Manuel; Martsenkovsky, Igor; Martin, Donna M.; Mane, Shrikant M.; Magnusson, Pall; Magalhaes, Tiago; Maestrini, Elena; Lowe, Jennifer K.; Lord, Catherine; Levitt, Pat; Martin, Christa Lese; Ledbetter, David H.; Leboyer, Marion; Lecouteur, Ann S.; Ladd-Acosta, Christine; Kolevzon, Alexander; Klauck, Sabine M.; Jacob, Suma; Iliadou, Bozenna; Hultman, Christina M.; Hougaard, David M.; Hertz-Picciotto, Irva; Hendren, Robert; Hansen, Christine Søholm; Haines, Jonathan L.; Guter, Stephen J.; Grice, Dorothy E.; Green, Jonathan M.; Green, Andrew; Goldberg, Arthur P.; Gillberg, Christopher; Gilbert, John; Gallagher, Louise; Freitag, Christine M.; Fombonne, Eric; Folstein, Susan E.; Fernandez, Bridget; Fallin, M. Daniele; Ercan-Sencicek, A. Gulhan; Ennis, Sean; Duque, Frederico; Duketis, Eftichia; Delorme, Richard; Derubeis, Silvia; Dejonge, Maretha V.; Dawson, Geraldine; Cuccaro, Michael L.; Correia, Catarina T.; Conroy, Judith; Conceição, Ines C.; Chiocchetti, Andreas G.; Celestino-Soper, Patrícia B.S.; Casey, Jillian; Cantor, Rita M.; Café, Cátia; Bybjerg-Grauholm, Jonas; Brennan, Sean; Bourgeron, Thomas; Bolton, Patrick F.; Bölte, Sven; Bolshakova, Nadia; Betancur, Catalina; Bernier, Raphael; Beaudet, Arthur L.; Battaglia, Agatino; Bal, Vanessa H.; Baird, Gillian; Bailey, Anthony J.; Bækvad-Hansen, Marie; Bader, Joel S.; Bacchelli, Elena; Anagnostou, Evdokia; Amaral, David; Almeida, Joana; Børglum, Anders D.; Buxbaum, Joseph D.; Chakravarti, Aravinda; Cook, Edwin H.; Coon, Hilary; Geschwind, Daniel H.; Gill, Michael; Hakonarson, Hakon; Hallmayer, Joachim; Palotie, Aarno; Santangelo, Susan; Sutcliffe, James S.; Arking, Dan E.; Devlin, Bernie; Daly, Mark J.
In:
Molecular Autism, Vol. 8, 21, 22.05.2017.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
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, Parr, JR, Pagnamenta, AT, Oliveira, G, Nurnberger, JI
, Nordentoft, M, Murtha, MT, Mouga, S, Mortensen, PB, Mors, O, Morrow, EM, Moreno-De-Luca, D, Monaco, AP, Minshew, N, Merikangas, A, McMahon, WM, McGrew, SG, Mattheisen, M, Martsenkovsky, I, Martin, DM, Mane, SM, Magnusson, P, Magalhaes, T, Maestrini, E, Lowe, JK, Lord, C, Levitt, P, Martin, CL, Ledbetter, DH, Leboyer, M, Lecouteur, AS, Ladd-Acosta, C, Kolevzon, A, Klauck, SM, Jacob, S, Iliadou, B, Hultman, CM, Hougaard, DM, Hertz-Picciotto, I, Hendren, R, Hansen, CS, Haines, JL, Guter, SJ, Grice, DE, Green, JM, Green, A, Goldberg, AP, Gillberg, C, Gilbert, J, Gallagher, L, Freitag, CM, Fombonne, E, Folstein, SE, Fernandez, B, Fallin, MD, Ercan-Sencicek, AG, Ennis, S, Duque, F, Duketis, E, Delorme, R, Derubeis, S, Dejonge, MV, Dawson, G, Cuccaro, ML, Correia, CT, Conroy, J, Conceição, IC, Chiocchetti, AG, Celestino-Soper, PBS, Casey, J, Cantor, RM, Café, C, Bybjerg-Grauholm, J, Brennan, S, Bourgeron, T, Bolton, PF, Bölte, S, Bolshakova, N, Betancur, C, Bernier, R, Beaudet, AL, Battaglia, A, Bal, VH, Baird, G, Bailey, AJ, Bækvad-Hansen, M, Bader, JS, Bacchelli, E, Anagnostou, E, Amaral, D, Almeida, J, Børglum, AD, Buxbaum, JD, Chakravarti, A, Cook, EH, Coon, H, Geschwind, DH, Gill, M, Hakonarson, H, Hallmayer, J, Palotie, A, Santangelo, S, Sutcliffe, JS, Arking, DE, Devlin, B & Daly, MJ 2017, '
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia',
Molecular Autism, vol. 8, 21.
https://doi.org/10.1186/s13229-017-0137-9APA
Anney, R. J. L., Ripke, S., Anttila, V., Grove, J., Holmans, P., Huang, H., Klei, L., Lee, P. H., Medland, S. E., Neale, B., Robinson, E., Weiss, L. A., Zwaigenbaum, L., Yu, T. W., Wittemeyer, K., Willsey, A. J., Wijsman, E. M.
, Werge, T., Wassink, T. H., ... Daly, M. J. (2017).
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
Molecular Autism,
8, [21].
https://doi.org/10.1186/s13229-017-0137-9Vancouver
Anney RJL, Ripke S, Anttila V, Grove J, Holmans P, Huang H et al.
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
Molecular Autism. 2017 May 22;8. 21.
https://doi.org/10.1186/s13229-017-0137-9Author
Anney, Richard J.L. ; Ripke, Stephan ; Anttila, Verneri ; Grove, Jakob ; Holmans, Peter ; Huang, Hailiang ; Klei, Lambertus ; Lee, Phil H. ; Medland, Sarah E. ; Neale, Benjamin ; Robinson, Elise ; Weiss, Lauren A. ; Zwaigenbaum, Lonnie ; Yu, Timothy W. ; Wittemeyer, Kerstin ; Willsey, A. Jeremy ; Wijsman, Ellen M. ; Werge, Thomas ; Wassink, Thomas H. ; Waltes, Regina ; Walsh, Christopher A. ; Wallace, Simon ; Vorstman, Jacob A.S. ; Vieland, Veronica J. ; Vicente, Astrid M. ; Vanengeland, Herman ; Tsang, Kathryn ; Thompson, Ann P. ; Szatmari, Peter ; Svantesson, Oscar ; Steinberg, Stacy ; Stefansson, Kari ; Stefansson, Hreinn ; State, Matthew W. ; Soorya, Latha ; Silagadze, Teimuraz ; Scherer, Stephen W. ; Schellenberg, Gerard D. ; Sandin, Sven ; Sanders, Stephan J. ; Saemundsen, Evald ; Rouleau, Guy A. ; Rogé, Bernadette ; Roeder, Kathryn ; Roberts, Wendy ; Reichert, Jennifer ; Reichenberg, Abraham ; Rehnström, Karola ; Regan, Regina ; Poustka, Fritz ; Poultney, Christopher S. ; Piven, Joseph ; Pinto, Dalila ; Pericak-Vance, Margaret A. ; Pejovic-Milovancevic, Milica ; Pedersen, Marianne Giørtz ; Pedersen, Carsten Bøcker ; Paterson, Andrew D. ; Parr, Jeremy R. ; Pagnamenta, Alistair T. ; Oliveira, Guiomar ; Nurnberger, John I. ; Nordentoft, Merete ; Murtha, Michael T. ; Mouga, Susana ; Mortensen, Preben Bo ; Mors, Ole ; Morrow, Eric M. ; Moreno-De-Luca, Daniel ; Monaco, Anthony P. ; Minshew, Nancy ; Merikangas, Alison ; McMahon, William M. ; McGrew, Susan G. ; Mattheisen, Manuel ; Martsenkovsky, Igor ; Martin, Donna M. ; Mane, Shrikant M. ; Magnusson, Pall ; Magalhaes, Tiago ; Maestrini, Elena ; Lowe, Jennifer K. ; Lord, Catherine ; Levitt, Pat ; Martin, Christa Lese ; Ledbetter, David H. ; Leboyer, Marion ; Lecouteur, Ann S. ; Ladd-Acosta, Christine ; Kolevzon, Alexander ; Klauck, Sabine M. ; Jacob, Suma ; Iliadou, Bozenna ; Hultman, Christina M. ; Hougaard, David M. ; Hertz-Picciotto, Irva ; Hendren, Robert ; Hansen, Christine Søholm ; Haines, Jonathan L. ; Guter, Stephen J. ; Grice, Dorothy E. ; Green, Jonathan M. ; Green, Andrew ; Goldberg, Arthur P. ; Gillberg, Christopher ; Gilbert, John ; Gallagher, Louise ; Freitag, Christine M. ; Fombonne, Eric ; Folstein, Susan E. ; Fernandez, Bridget ; Fallin, M. Daniele ; Ercan-Sencicek, A. Gulhan ; Ennis, Sean ; Duque, Frederico ; Duketis, Eftichia ; Delorme, Richard ; Derubeis, Silvia ; Dejonge, Maretha V. ; Dawson, Geraldine ; Cuccaro, Michael L. ; Correia, Catarina T. ; Conroy, Judith ; Conceição, Ines C. ; Chiocchetti, Andreas G. ; Celestino-Soper, Patrícia B.S. ; Casey, Jillian ; Cantor, Rita M. ; Café, Cátia ; Bybjerg-Grauholm, Jonas ; Brennan, Sean ; Bourgeron, Thomas ; Bolton, Patrick F. ; Bölte, Sven ; Bolshakova, Nadia ; Betancur, Catalina ; Bernier, Raphael ; Beaudet, Arthur L. ; Battaglia, Agatino ; Bal, Vanessa H. ; Baird, Gillian ; Bailey, Anthony J. ; Bækvad-Hansen, Marie ; Bader, Joel S. ; Bacchelli, Elena ; Anagnostou, Evdokia ; Amaral, David ; Almeida, Joana ; Børglum, Anders D. ; Buxbaum, Joseph D. ; Chakravarti, Aravinda ; Cook, Edwin H. ; Coon, Hilary ; Geschwind, Daniel H. ; Gill, Michael ; Hakonarson, Hakon ; Hallmayer, Joachim ; Palotie, Aarno ; Santangelo, Susan ; Sutcliffe, James S. ; Arking, Dan E. ; Devlin, Bernie ; Daly, Mark J. / 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. In: Molecular Autism. 2017 ; Vol. 8.
Bibtex
@article{aee5c4ea0d4d41ae9b88ea97fca45ef2,
title = "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",
abstract = "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) <1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10-6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.",
keywords = "Autism spectrum disorder, Gene-set analysis, Genetic correlation, Genome-wide association study, Heritability, Meta-analysis, Neurodevelopment, Schizophrenia",
author = "Anney, {Richard J.L.} and Stephan Ripke and Verneri Anttila and Jakob Grove and Peter Holmans and Hailiang Huang and Lambertus Klei and Lee, {Phil H.} and Medland, {Sarah E.} and Benjamin Neale and Elise Robinson and Weiss, {Lauren A.} and Lonnie Zwaigenbaum and Yu, {Timothy W.} and Kerstin Wittemeyer and Willsey, {A. Jeremy} and Wijsman, {Ellen M.} and Thomas Werge and Wassink, {Thomas H.} and Regina Waltes and Walsh, {Christopher A.} and Simon Wallace and Vorstman, {Jacob A.S.} and Vieland, {Veronica J.} and Vicente, {Astrid M.} and Herman Vanengeland and Kathryn Tsang and Thompson, {Ann P.} and Peter Szatmari and Oscar Svantesson and Stacy Steinberg and Kari Stefansson and Hreinn Stefansson and State, {Matthew W.} and Latha Soorya and Teimuraz Silagadze and Scherer, {Stephen W.} and Schellenberg, {Gerard D.} and Sven Sandin and Sanders, {Stephan J.} and Evald Saemundsen and Rouleau, {Guy A.} and Bernadette Rog{\'e} and Kathryn Roeder and Wendy Roberts and Jennifer Reichert and Abraham Reichenberg and Karola Rehnstr{\"o}m and Regina Regan and Fritz Poustka and Poultney, {Christopher S.} and Joseph Piven and Dalila Pinto and Pericak-Vance, {Margaret A.} and Milica Pejovic-Milovancevic and Pedersen, {Marianne Gi{\o}rtz} and Pedersen, {Carsten B{\o}cker} and Paterson, {Andrew D.} and Parr, {Jeremy R.} and Pagnamenta, {Alistair T.} and Guiomar Oliveira and Nurnberger, {John I.} and Merete Nordentoft and Murtha, {Michael T.} and Susana Mouga and Mortensen, {Preben Bo} and Ole Mors and Morrow, {Eric M.} and Daniel Moreno-De-Luca and Monaco, {Anthony P.} and Nancy Minshew and Alison Merikangas and McMahon, {William M.} and McGrew, {Susan G.} and Manuel Mattheisen and Igor Martsenkovsky and Martin, {Donna M.} and Mane, {Shrikant M.} and Pall Magnusson and Tiago Magalhaes and Elena Maestrini and Lowe, {Jennifer K.} and Catherine Lord and Pat Levitt and Martin, {Christa Lese} and Ledbetter, {David H.} and Marion Leboyer and Lecouteur, {Ann S.} and Christine Ladd-Acosta and Alexander Kolevzon and Klauck, {Sabine M.} and Suma Jacob and Bozenna Iliadou and Hultman, {Christina M.} and Hougaard, {David M.} and Irva Hertz-Picciotto and Robert Hendren and Hansen, {Christine S{\o}holm} and Haines, {Jonathan L.} and Guter, {Stephen J.} and Grice, {Dorothy E.} and Green, {Jonathan M.} and Andrew Green and Goldberg, {Arthur P.} and Christopher Gillberg and John Gilbert and Louise Gallagher and Freitag, {Christine M.} and Eric Fombonne and Folstein, {Susan E.} and Bridget Fernandez and Fallin, {M. Daniele} and Ercan-Sencicek, {A. Gulhan} and Sean Ennis and Frederico Duque and Eftichia Duketis and Richard Delorme and Silvia Derubeis and Dejonge, {Maretha V.} and Geraldine Dawson and Cuccaro, {Michael L.} and Correia, {Catarina T.} and Judith Conroy and Concei{\c c}{\~a}o, {Ines C.} and Chiocchetti, {Andreas G.} and Celestino-Soper, {Patr{\'i}cia B.S.} and Jillian Casey and Cantor, {Rita M.} and C{\'a}tia Caf{\'e} and Jonas Bybjerg-Grauholm and Sean Brennan and Thomas Bourgeron and Bolton, {Patrick F.} and Sven B{\"o}lte and Nadia Bolshakova and Catalina Betancur and Raphael Bernier and Beaudet, {Arthur L.} and Agatino Battaglia and Bal, {Vanessa H.} and Gillian Baird and Bailey, {Anthony J.} and Marie B{\ae}kvad-Hansen and Bader, {Joel S.} and Elena Bacchelli and Evdokia Anagnostou and David Amaral and Joana Almeida and B{\o}rglum, {Anders D.} and Buxbaum, {Joseph D.} and Aravinda Chakravarti and Cook, {Edwin H.} and Hilary Coon and Geschwind, {Daniel H.} and Michael Gill and Hakon Hakonarson and Joachim Hallmayer and Aarno Palotie and Susan Santangelo and Sutcliffe, {James S.} and Arking, {Dan E.} and Bernie Devlin and Daly, {Mark J.}",
year = "2017",
month = may,
day = "22",
doi = "10.1186/s13229-017-0137-9",
language = "English",
volume = "8",
journal = "Molecular Autism",
issn = "2040-2392",
publisher = "BioMed Central Ltd.",
}
RIS
TY - JOUR
T1 - 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
AU - Anney, Richard J.L.
AU - Ripke, Stephan
AU - Anttila, Verneri
AU - Grove, Jakob
AU - Holmans, Peter
AU - Huang, Hailiang
AU - Klei, Lambertus
AU - Lee, Phil H.
AU - Medland, Sarah E.
AU - Neale, Benjamin
AU - Robinson, Elise
AU - Weiss, Lauren A.
AU - Zwaigenbaum, Lonnie
AU - Yu, Timothy W.
AU - Wittemeyer, Kerstin
AU - Willsey, A. Jeremy
AU - Wijsman, Ellen M.
AU - Werge, Thomas
AU - Wassink, Thomas H.
AU - Waltes, Regina
AU - Walsh, Christopher A.
AU - Wallace, Simon
AU - Vorstman, Jacob A.S.
AU - Vieland, Veronica J.
AU - Vicente, Astrid M.
AU - Vanengeland, Herman
AU - Tsang, Kathryn
AU - Thompson, Ann P.
AU - Szatmari, Peter
AU - Svantesson, Oscar
AU - Steinberg, Stacy
AU - Stefansson, Kari
AU - Stefansson, Hreinn
AU - State, Matthew W.
AU - Soorya, Latha
AU - Silagadze, Teimuraz
AU - Scherer, Stephen W.
AU - Schellenberg, Gerard D.
AU - Sandin, Sven
AU - Sanders, Stephan J.
AU - Saemundsen, Evald
AU - Rouleau, Guy A.
AU - Rogé, Bernadette
AU - Roeder, Kathryn
AU - Roberts, Wendy
AU - Reichert, Jennifer
AU - Reichenberg, Abraham
AU - Rehnström, Karola
AU - Regan, Regina
AU - Poustka, Fritz
AU - Poultney, Christopher S.
AU - Piven, Joseph
AU - Pinto, Dalila
AU - Pericak-Vance, Margaret A.
AU - Pejovic-Milovancevic, Milica
AU - Pedersen, Marianne Giørtz
AU - Pedersen, Carsten Bøcker
AU - Paterson, Andrew D.
AU - Parr, Jeremy R.
AU - Pagnamenta, Alistair T.
AU - Oliveira, Guiomar
AU - Nurnberger, John I.
AU - Nordentoft, Merete
AU - Murtha, Michael T.
AU - Mouga, Susana
AU - Mortensen, Preben Bo
AU - Mors, Ole
AU - Morrow, Eric M.
AU - Moreno-De-Luca, Daniel
AU - Monaco, Anthony P.
AU - Minshew, Nancy
AU - Merikangas, Alison
AU - McMahon, William M.
AU - McGrew, Susan G.
AU - Mattheisen, Manuel
AU - Martsenkovsky, Igor
AU - Martin, Donna M.
AU - Mane, Shrikant M.
AU - Magnusson, Pall
AU - Magalhaes, Tiago
AU - Maestrini, Elena
AU - Lowe, Jennifer K.
AU - Lord, Catherine
AU - Levitt, Pat
AU - Martin, Christa Lese
AU - Ledbetter, David H.
AU - Leboyer, Marion
AU - Lecouteur, Ann S.
AU - Ladd-Acosta, Christine
AU - Kolevzon, Alexander
AU - Klauck, Sabine M.
AU - Jacob, Suma
AU - Iliadou, Bozenna
AU - Hultman, Christina M.
AU - Hougaard, David M.
AU - Hertz-Picciotto, Irva
AU - Hendren, Robert
AU - Hansen, Christine Søholm
AU - Haines, Jonathan L.
AU - Guter, Stephen J.
AU - Grice, Dorothy E.
AU - Green, Jonathan M.
AU - Green, Andrew
AU - Goldberg, Arthur P.
AU - Gillberg, Christopher
AU - Gilbert, John
AU - Gallagher, Louise
AU - Freitag, Christine M.
AU - Fombonne, Eric
AU - Folstein, Susan E.
AU - Fernandez, Bridget
AU - Fallin, M. Daniele
AU - Ercan-Sencicek, A. Gulhan
AU - Ennis, Sean
AU - Duque, Frederico
AU - Duketis, Eftichia
AU - Delorme, Richard
AU - Derubeis, Silvia
AU - Dejonge, Maretha V.
AU - Dawson, Geraldine
AU - Cuccaro, Michael L.
AU - Correia, Catarina T.
AU - Conroy, Judith
AU - Conceição, Ines C.
AU - Chiocchetti, Andreas G.
AU - Celestino-Soper, Patrícia B.S.
AU - Casey, Jillian
AU - Cantor, Rita M.
AU - Café, Cátia
AU - Bybjerg-Grauholm, Jonas
AU - Brennan, Sean
AU - Bourgeron, Thomas
AU - Bolton, Patrick F.
AU - Bölte, Sven
AU - Bolshakova, Nadia
AU - Betancur, Catalina
AU - Bernier, Raphael
AU - Beaudet, Arthur L.
AU - Battaglia, Agatino
AU - Bal, Vanessa H.
AU - Baird, Gillian
AU - Bailey, Anthony J.
AU - Bækvad-Hansen, Marie
AU - Bader, Joel S.
AU - Bacchelli, Elena
AU - Anagnostou, Evdokia
AU - Amaral, David
AU - Almeida, Joana
AU - Børglum, Anders D.
AU - Buxbaum, Joseph D.
AU - Chakravarti, Aravinda
AU - Cook, Edwin H.
AU - Coon, Hilary
AU - Geschwind, Daniel H.
AU - Gill, Michael
AU - Hakonarson, Hakon
AU - Hallmayer, Joachim
AU - Palotie, Aarno
AU - Santangelo, Susan
AU - Sutcliffe, James S.
AU - Arking, Dan E.
AU - Devlin, Bernie
AU - Daly, Mark J.
PY - 2017/5/22
Y1 - 2017/5/22
N2 - 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) <1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10-6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
AB - 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) <1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10-6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
KW - Autism spectrum disorder
KW - Gene-set analysis
KW - Genetic correlation
KW - Genome-wide association study
KW - Heritability
KW - Meta-analysis
KW - Neurodevelopment
KW - Schizophrenia
U2 - 10.1186/s13229-017-0137-9
DO - 10.1186/s13229-017-0137-9
M3 - Journal article
C2 - 28540026
AN - SCOPUS:85019753129
VL - 8
JO - Molecular Autism
JF - Molecular Autism
SN - 2040-2392
M1 - 21
ER -
