Mapping autism risk loci using genetic linkage and chromosomal rearrangements

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; Frederike Koop; Marjolijn Langemeijer; 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

doi:10.1038/ng1985

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

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 GoedkenAlberto 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, Frederike Koop, Marjolijn Langemeijer, 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

Research output: Contribution to journal › Article › peer-review

1156 Scopus citations

Abstract

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 1,168 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.

Original language	English (US)
Pages (from-to)	319-328
Number of pages	10
Journal	Nature genetics
Volume	39
Issue number	3
DOIs	https://doi.org/10.1038/ng1985
State	Published - Mar 2007
Externally published	Yes

ASJC Scopus subject areas

Genetics

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10.1038/ng1985

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Szatmari, P., Paterson, A. D., Zwaigenbaum, L., Roberts, W., Brian, J., Liu, X. Q., Vincent, J. B., Skaug, J. L., Thompson, A. P., Senman, L., Feuk, L., Qian, C., Bryson, S. E., Jones, M. B., Marshall, C. R., Scherer, S. W., Vieland, V. J., Bartlett, C., Mangin, L. V., ... Shih, A. (2007). Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature genetics, 39(3), 319-328. https://doi.org/10.1038/ng1985

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, Rogé, B, Mantoulan, C, Wittemeyer, K, Poustka, A, Felder, B, Klauck, SM, Schuster, C, Poustka, F, Bölte, S, Feineis-Matthews, S, Herbrecht, E, Schmötzer, 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 & Shih, A 2007, 'Mapping autism risk loci using genetic linkage and chromosomal rearrangements', Nature genetics, vol. 39, no. 3, pp. 319-328. https://doi.org/10.1038/ng1985

@article{b1e558b62a2740f19fc52a81e92d41fa,

title = "Mapping autism risk loci using genetic linkage and chromosomal rearrangements",

abstract = "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 1,168 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.",

author = "Peter Szatmari and Paterson, {Andrew D.} and Lonnie Zwaigenbaum and Wendy Roberts and Jessica Brian and Liu, {Xiao Qing} and Vincent, {John B.} and Skaug, {Jennifer L.} and Thompson, {Ann P.} and Lili Senman and Lars Feuk and Cheng Qian and Bryson, {Susan E.} and Jones, {Marshall B.} and Marshall, {Christian R.} and Scherer, {Stephen W.} and Vieland, {Veronica J.} and Christopher Bartlett and Mangin, {La Vonne} and Rhinda Goedken and Alberto Segre and Pericak-Vance, {Margaret A.} and Cuccaro, {Michael L.} and Gilbert, {John R.} and Wright, {Harry H.} and Abramson, {Ruth K.} and Catalina Betancur and Thomas Bourgeron and Christopher Gillberg and Marion Leboyer and Buxbaum, {Joseph D.} and Davis, {Kenneth L.} and Eric Hollander and Silverman, {Jeremy M.} and Joachim Hallmayer and Linda Lotspeich and Sutcliffe, {James S.} and Haines, {Jonathan L.} and Folstein, {Susan E.} and Joseph Piven and Wassink, {Thomas H.} and Val Sheffield and Geschwind, {Daniel H.} and Maja Bucan and Brown, {W. Ted} and Cantor, {Rita M.} and Constantino, {John N.} and Gilliam, {T. Conrad} and Martha Herbert and Clara LaJonchere and Ledbetter, {David H.} and Christa Lese-Martin and Janet Miller and Stan Nelson and Samango-Sprouse, {Carol A.} and Sarah Spence and Matthew State and Tanzi, {Rudolph E.} and Hilary Coon and Geraldine Dawson and Bernie Devlin and Annette Estes and Pamela Flodman and Lambertus Klei and McMahon, {William M.} and Nancy Minshew and Jeff Munson and Elena Korvatska and Rodier, {Patricia M.} and Schellenberg, {Gerard D.} and Moyra Smith and Spence, {M. Anne} and Chris Stodgell and Tepper, {Ping Guo} and Wijsman, {Ellen M.} and Yu, {Chang En} and Bernadette Rog{\'e} and Carine Mantoulan and Kerstin Wittemeyer and Annemarie Poustka and B{\"a}rbel Felder and Klauck, {Sabine M.} and Claudia Schuster and Fritz Poustka and Sven B{\"o}lte and Sabine Feineis-Matthews and Evelyn Herbrecht and Gabi Schm{\"o}tzer and John Tsiantis and Katerina Papanikolaou and Elena Maestrini and Elena Bacchelli and Francesca Blasi and Simona Carone and Claudio Toma and {Van Engeland}, Herman and {De Jonge}, Maretha and Chantal Kemner and Frederike Koop and Marjolijn Langemeijer and Channa Hijimans and Staal, {Wouter G.} and Gillian Baird and Bolton, {Patrick F.} and Rutter, {Michael L.} and Emma Weisblatt and Jonathan Green and Catherine Aldred and Wilkinson, {Julie Anne} and Andrew Pickles and {Le Couteur}, Ann and Tom Berney and Helen McConachie and Bailey, {Anthony J.} and Kostas Francis and Gemma Honeyman and Aislinn Hutchinson and Parr, {Jeremy R.} and Simon Wallace and Monaco, {Anthony P.} and Gabrielle Barnby and Kazuhiro Kobayashi and Lamb, {Janine A.} and Ines Sousa and Nuala Sykes and Cook, {Edwin H.} and Guter, {Stephen J.} and Leventhal, {Bennett L.} and Jeff Salt and Catherine Lord and Christina Corsello and Vanessa Hus and Weeks, {Daniel E.} and Fred Volkmar and Ma{\"i}t{\'e} Tauber and Eric Fombonne and Andy Shih",

note = "Funding Information: The authors are indebted to the participating families for their contribution of time and effort in support of this study. We gratefully acknowledge Autism Speaks, formerly the National Alliance for Autism Research, for financial support for data pooling, SNP genotyping and data analysis. The Autism Genetics Cooperative thanks Assistance Publique-H{\^o}pitaux de Paris, Canadian Institutes for Health Research (CIHR grant 11350 to P.S.), Catherine and Maxwell Meighan Foundation, Fondation de France, Fondation France T{\'e}l{\'e}com, Fondation pour la Recherche M{\'e}dicale, Genome Canada/Ontario Genomics Institute, The Hospital for Sick Children Foundation, Howard Hughes Medical Institute, INSERM, McLaughlin Centre for Molecular Medicine, National Institute of Child Health and Human Development, National Institute of Mental Health (MH066673 to J.D.B.; MH55135 to S.E.F.; MH52708 to N. Risch (University of California, San Francisco); MH061009 to J.S.S.), National Institute of Neurological Disorders and Stroke (NS042165 to J.H.; NS026630 and NS036738 to M.A.P.-V.; NS049261 to J.S.S.; NS043550 to T.H.W.), Swedish Science Council, Seaver Autism Research Foundation and The Centre for Applied Genomics (Toronto). S.W.S. is an Investigator of the CIHR and an HHMI International Scholar. The Autism Genetic Resource Exchange Consortium gratefully acknowledges the resources provided by the participating families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by the National Institute of Mental Health (MH64547 to D.H.G.). The Collaborative Programs of Excellence thank the National Center for Research Resources (M01-RR00064), National Institute of Child Health and Human Development (U19HD34565 G.D. and G.S.), NIMH (MH057881), NINDS (5 U19 HD035476 to W.M.McM.) and the Utah Autism Foundation. Funding Information: The International Molecular Genetic Study of Autism Consortium thanks the UK Medical Research Council, Wellcome Trust, BIOMED 2 (CT-97-2759), EC Fifth Framework (QLG2-CT-1999-0094), Telethon-Italy (GGP030227), Janus Korczak Foundation, Deutsche Forschungsgemeinschaft, Fondation France Telecom, Conseil Regional Midi-Pyrenees, Danish Medical Research Council, Sofiefonden, Beatrice Surovell Haskells Fond for Child Mental Health Research of Copenhagen, Danish Natural Science Research Council (9802210) and the US National Institutes of Health (U19 HD35482, MO1 RR06022, K05 MH01196, K02 MH01389). A.J.B. is the Cheryl and Reece Scott Professor of Psychiatry. A.P.M. is a Wellcome Trust Principal Research Fellow. Requests for data or methods should be addressed to B.D. (devlinbj@upmc.edu) or S.W.S. (steve@genet.sickkids.on.ca). AUTHOR CONTRIBUTIONS P.S., A.D.P., S.W.S., V.J.V., M.A.P.-V., C.B., J.D.B., J.H., J.S.S., J.H., J.L.H., J.P., T.H.W., D.H.G., R.C., S.N., G.D., G.D.S., B.D., W.M.M., E.M.W., A.J.B., A.P.M. and E.H.C. were lead AGP investigators and contributed equally to this project. The Autism Genome Project (AGP). The AGP comprises four existing consortia of partners or countries (listed alphabetically below).",

year = "2007",

month = mar,

doi = "10.1038/ng1985",

language = "English (US)",

volume = "39",

pages = "319--328",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - Mapping autism risk loci using genetic linkage and chromosomal rearrangements

AU - Szatmari, Peter

AU - Paterson, Andrew D.

AU - Zwaigenbaum, Lonnie

AU - Roberts, Wendy

AU - Brian, Jessica

AU - Liu, Xiao Qing

AU - Vincent, John B.

AU - Skaug, Jennifer L.

AU - Thompson, Ann P.

AU - Senman, Lili

AU - Feuk, Lars

AU - Qian, Cheng

AU - Bryson, Susan E.

AU - Jones, Marshall B.

AU - Marshall, Christian R.

AU - Scherer, Stephen W.

AU - Vieland, Veronica J.

AU - Bartlett, Christopher

AU - Mangin, La Vonne

AU - Goedken, Rhinda

AU - Segre, Alberto

AU - Pericak-Vance, Margaret A.

AU - Cuccaro, Michael L.

AU - Gilbert, John R.

AU - Wright, Harry H.

AU - Abramson, Ruth K.

AU - Betancur, Catalina

AU - Bourgeron, Thomas

AU - Gillberg, Christopher

AU - Leboyer, Marion

AU - Buxbaum, Joseph D.

AU - Davis, Kenneth L.

AU - Hollander, Eric

AU - Silverman, Jeremy M.

AU - Hallmayer, Joachim

AU - Lotspeich, Linda

AU - Sutcliffe, James S.

AU - Haines, Jonathan L.

AU - Folstein, Susan E.

AU - Piven, Joseph

AU - Wassink, Thomas H.

AU - Sheffield, Val

AU - Geschwind, Daniel H.

AU - Bucan, Maja

AU - Brown, W. Ted

AU - Cantor, Rita M.

AU - Constantino, John N.

AU - Gilliam, T. Conrad

AU - Herbert, Martha

AU - LaJonchere, Clara

AU - Ledbetter, David H.

AU - Lese-Martin, Christa

AU - Miller, Janet

AU - Nelson, Stan

AU - Samango-Sprouse, Carol A.

AU - Spence, Sarah

AU - State, Matthew

AU - Tanzi, Rudolph E.

AU - Coon, Hilary

AU - Dawson, Geraldine

AU - Devlin, Bernie

AU - Estes, Annette

AU - Flodman, Pamela

AU - Klei, Lambertus

AU - McMahon, William M.

AU - Minshew, Nancy

AU - Munson, Jeff

AU - Korvatska, Elena

AU - Rodier, Patricia M.

AU - Schellenberg, Gerard D.

AU - Smith, Moyra

AU - Spence, M. Anne

AU - Stodgell, Chris

AU - Tepper, Ping Guo

AU - Wijsman, Ellen M.

AU - Yu, Chang En

AU - Rogé, Bernadette

AU - Mantoulan, Carine

AU - Wittemeyer, Kerstin

AU - Poustka, Annemarie

AU - Felder, Bärbel

AU - Klauck, Sabine M.

AU - Schuster, Claudia

AU - Poustka, Fritz

AU - Bölte, Sven

AU - Feineis-Matthews, Sabine

AU - Herbrecht, Evelyn

AU - Schmötzer, Gabi

AU - Tsiantis, John

AU - Papanikolaou, Katerina

AU - Maestrini, Elena

AU - Bacchelli, Elena

AU - Blasi, Francesca

AU - Carone, Simona

AU - Toma, Claudio

AU - Van Engeland, Herman

AU - De Jonge, Maretha

AU - Kemner, Chantal

AU - Koop, Frederike

AU - Langemeijer, Marjolijn

AU - Hijimans, Channa

AU - Staal, Wouter G.

AU - Baird, Gillian

AU - Bolton, Patrick F.

AU - Rutter, Michael L.

AU - Weisblatt, Emma

AU - Green, Jonathan

AU - Aldred, Catherine

AU - Wilkinson, Julie Anne

AU - Pickles, Andrew

AU - Le Couteur, Ann

AU - Berney, Tom

AU - McConachie, Helen

AU - Bailey, Anthony J.

AU - Francis, Kostas

AU - Honeyman, Gemma

AU - Hutchinson, Aislinn

AU - Parr, Jeremy R.

AU - Wallace, Simon

AU - Monaco, Anthony P.

AU - Barnby, Gabrielle

AU - Kobayashi, Kazuhiro

AU - Lamb, Janine A.

AU - Sousa, Ines

AU - Sykes, Nuala

AU - Cook, Edwin H.

AU - Guter, Stephen J.

AU - Leventhal, Bennett L.

AU - Salt, Jeff

AU - Lord, Catherine

AU - Corsello, Christina

AU - Hus, Vanessa

AU - Weeks, Daniel E.

AU - Volkmar, Fred

AU - Tauber, Maïté

AU - Fombonne, Eric

AU - Shih, Andy

N1 - Funding Information: The authors are indebted to the participating families for their contribution of time and effort in support of this study. We gratefully acknowledge Autism Speaks, formerly the National Alliance for Autism Research, for financial support for data pooling, SNP genotyping and data analysis. The Autism Genetics Cooperative thanks Assistance Publique-Hôpitaux de Paris, Canadian Institutes for Health Research (CIHR grant 11350 to P.S.), Catherine and Maxwell Meighan Foundation, Fondation de France, Fondation France Télécom, Fondation pour la Recherche Médicale, Genome Canada/Ontario Genomics Institute, The Hospital for Sick Children Foundation, Howard Hughes Medical Institute, INSERM, McLaughlin Centre for Molecular Medicine, National Institute of Child Health and Human Development, National Institute of Mental Health (MH066673 to J.D.B.; MH55135 to S.E.F.; MH52708 to N. Risch (University of California, San Francisco); MH061009 to J.S.S.), National Institute of Neurological Disorders and Stroke (NS042165 to J.H.; NS026630 and NS036738 to M.A.P.-V.; NS049261 to J.S.S.; NS043550 to T.H.W.), Swedish Science Council, Seaver Autism Research Foundation and The Centre for Applied Genomics (Toronto). S.W.S. is an Investigator of the CIHR and an HHMI International Scholar. The Autism Genetic Resource Exchange Consortium gratefully acknowledges the resources provided by the participating families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by the National Institute of Mental Health (MH64547 to D.H.G.). The Collaborative Programs of Excellence thank the National Center for Research Resources (M01-RR00064), National Institute of Child Health and Human Development (U19HD34565 G.D. and G.S.), NIMH (MH057881), NINDS (5 U19 HD035476 to W.M.McM.) and the Utah Autism Foundation. Funding Information: The International Molecular Genetic Study of Autism Consortium thanks the UK Medical Research Council, Wellcome Trust, BIOMED 2 (CT-97-2759), EC Fifth Framework (QLG2-CT-1999-0094), Telethon-Italy (GGP030227), Janus Korczak Foundation, Deutsche Forschungsgemeinschaft, Fondation France Telecom, Conseil Regional Midi-Pyrenees, Danish Medical Research Council, Sofiefonden, Beatrice Surovell Haskells Fond for Child Mental Health Research of Copenhagen, Danish Natural Science Research Council (9802210) and the US National Institutes of Health (U19 HD35482, MO1 RR06022, K05 MH01196, K02 MH01389). A.J.B. is the Cheryl and Reece Scott Professor of Psychiatry. A.P.M. is a Wellcome Trust Principal Research Fellow. Requests for data or methods should be addressed to B.D. (devlinbj@upmc.edu) or S.W.S. (steve@genet.sickkids.on.ca). AUTHOR CONTRIBUTIONS P.S., A.D.P., S.W.S., V.J.V., M.A.P.-V., C.B., J.D.B., J.H., J.S.S., J.H., J.L.H., J.P., T.H.W., D.H.G., R.C., S.N., G.D., G.D.S., B.D., W.M.M., E.M.W., A.J.B., A.P.M. and E.H.C. were lead AGP investigators and contributed equally to this project. The Autism Genome Project (AGP). The AGP comprises four existing consortia of partners or countries (listed alphabetically below).

PY - 2007/3

Y1 - 2007/3

N2 - 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 1,168 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.

AB - 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 1,168 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.

UR - http://www.scopus.com/inward/record.url?scp=33847327313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847327313&partnerID=8YFLogxK

U2 - 10.1038/ng1985

DO - 10.1038/ng1985

M3 - Article

C2 - 17322880

AN - SCOPUS:33847327313

SN - 1061-4036

VL - 39

SP - 319

EP - 328

JO - Nature genetics

JF - Nature genetics

IS - 3

ER -

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

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