A genome-wide scan for common alleles affecting risk for autism

Richard Anney; Lambertus Klei; Dalila Pinto; Regina Regan; Judith Conroy; Tiago R. Magalhaes; Catarina Correia; Brett S. Abrahams; Nuala Sykes; Alistair T. Pagnamenta; Joana Almeida; Elena Bacchelli; Anthony J. Bailey; Gillian Baird; Agatino Battaglia; Tom Berney; Nadia Bolshakova; Sven Boelte; Patrick F. Bolton; Thomas Bourgeron; Sean Brennan; Jessica Brian; Andrew R. Carson; Guillermo Casallo; Jillian Casey; Su H. Chu; Lynne Cochrane; Christina Corsello; Emily L. Crawford; Andrew Crossett; Geraldine Dawson; Maretha de Jonge; Richard Delorme; Irene Drmic; Eftichia Duketis; Frederico Duque; Annette Estes; Penny Farrar; Bridget A. Fernandez; Susan E. Folstein; Eric Fombonne; Christine M. Freitag; John Gilbert; Christopher Gillberg; Joseph T. Glessner; Jeremy Goldberg; Jonathan Green; Stephen J. Guter; Hakon Hakonarson; Elizabeth A. Heron; Matthew Hill; Richard Holt; Jennifer L. Howe; Gillian Hughes; Vanessa Hus; Roberta Igliozzi; Cecilia Kim; Sabine M. Klauck; Alexander Kolevzon; Olena Korvatska; Vlad Kustanovich; Clara M. Lajonchere; Janine A. Lamb; Magdalena Laskawiec; Marion Leboyer; Ann Le Couteur; Bennett L. Leventhal; Anath C. Lionel; Xiao-Qing Liu; Catherine Lord; Linda Lotspeich; Sabata C. Lund; Elena Maestrini; William Mahoney; Carine Mantoulan; Christian R. Marshall; Helen McConachie; Christopher J. McDougle; Jane McGrath; William M. McMahon; Nadine M. Melhem; Alison Merikangas; Ohsuke Migita; Nancy J. Minshew; Ghazala K. Mirza; Jeff Munson; Stanley F. Nelson; Carolyn Noakes; Abdul Noor; Gudrun Nygren; Guiomar Oliveira; Katerina Papanikolaou; Jeremy R. Parr; Barbara Parrini; Tara Paton; Andrew Pickles; Joseph Piven; David J. osey; Annemarie Poustka; Fritz Poustka; Aparna Prasad; Jiannis Ragoussis; Katy Renshaw; Jessica Rickaby; Wendy Roberts; Kathryn Roeder; Bernadette Roge; Michael L. Rutter; Laura J. Bierut; John P. Rice; Jeff Salt; Katherine Sansom; Daisuke Sato; Ricardo Segurado; Lili Senman; Naisha Shah; Val C. Sheffield; Latha Soorya; Ines Sousa; Vera Stoppioni; Christina Strawbridge; Raffaella Tancredi; Katherine Tansey; Bhooma Thiruvahindrapduram; Ann P. Thompson; Susanne Thomson; Ana Tryfon; John Tsiantis; Herman Van Engeland; John B. Vincent; Fred Volkmar; Simon Wallace; Kai Wang; Zhouzhi Wang; Thomas H. Wassink; Kirsty Wing; Kerstin Wittemeyer; Shawn Wood; Brian L. Yaspan; Danielle Zurawiecki; Lonnie Zwaigenbaum; Catalina Betancur; Joseph D. Buxbaum; Rita M. Cantor; Edwin H. Cook; Hilary Coon; Michael L. Cuccaro; Louise Gallagher; Daniel H. Geschwind; Michael Gill; Jonathan L. Haines; Judith Miller; Anthony P. Monaco; John I. Nurnberger; Andrew D. Paterson; Margaret A. Pericak-Vance; Gerard D. Schellenberg; Stephen W. Scherer; James S. Sutcliffe; Peter Szatmari; Astrid M. Vicente; Veronica J. Vieland; Ellen M. Wijsman; Bernie Devlin; Sean Ennis; Joachim Hallmayer

doi:10.1093/hmg/ddq307

A genome-wide scan for common alleles affecting risk for autism

Richard Anney, Lambertus Klei, Dalila Pinto, Regina Regan, Judith Conroy, Tiago R. Magalhaes, Catarina Correia, Brett S. Abrahams, Nuala Sykes, Alistair T. Pagnamenta, Joana Almeida, Elena Bacchelli, Anthony J. Bailey, Gillian Baird, Agatino Battaglia, Tom Berney, Nadia Bolshakova, Sven Boelte, Patrick F. Bolton, Thomas BourgeronSean Brennan, Jessica Brian, Andrew R. Carson, Guillermo Casallo, Jillian Casey, Su H. Chu, Lynne Cochrane, Christina Corsello, Emily L. Crawford, Andrew Crossett, Geraldine Dawson, Maretha de Jonge, Richard Delorme, Irene Drmic, Eftichia Duketis, Frederico Duque, Annette Estes, Penny Farrar, Bridget A. Fernandez, Susan E. Folstein, Eric Fombonne, Christine M. Freitag, John Gilbert, Christopher Gillberg, Joseph T. Glessner, Jeremy Goldberg, Jonathan Green, Stephen J. Guter, Hakon Hakonarson, Elizabeth A. Heron, Matthew Hill, Richard Holt, Jennifer L. Howe, Gillian Hughes, Vanessa Hus, Roberta Igliozzi, Cecilia Kim, Sabine M. Klauck, Alexander Kolevzon, Olena Korvatska, Vlad Kustanovich, Clara M. Lajonchere, Janine A. Lamb, Magdalena Laskawiec, Marion Leboyer, Ann Le Couteur, Bennett L. Leventhal, Anath C. Lionel, Xiao-Qing Liu, Catherine Lord, Linda Lotspeich, Sabata C. Lund, Elena Maestrini, William Mahoney, Carine Mantoulan, Christian R. Marshall, Helen McConachie, Christopher J. McDougle, Jane McGrath, William M. McMahon, Nadine M. Melhem, Alison Merikangas, Ohsuke Migita, Nancy J. Minshew, Ghazala K. Mirza, Jeff Munson, Stanley F. Nelson, Carolyn Noakes, Abdul Noor, Gudrun Nygren, Guiomar Oliveira, Katerina Papanikolaou, Jeremy R. Parr, Barbara Parrini, Tara Paton, Andrew Pickles, Joseph Piven, David J. osey, Annemarie Poustka, Fritz Poustka, Aparna Prasad, Jiannis Ragoussis, Katy Renshaw, Jessica Rickaby, Wendy Roberts, Kathryn Roeder, Bernadette Roge, Michael L. Rutter, Laura J. Bierut, John P. Rice, Jeff Salt, Katherine Sansom, Daisuke Sato, Ricardo Segurado, Lili Senman, Naisha Shah, Val C. Sheffield, Latha Soorya, Ines Sousa, Vera Stoppioni, Christina Strawbridge, Raffaella Tancredi, Katherine Tansey, Bhooma Thiruvahindrapduram, Ann P. Thompson, Susanne Thomson, Ana Tryfon, John Tsiantis, Herman Van Engeland, John B. Vincent, Fred Volkmar, Simon Wallace, Kai Wang, Zhouzhi Wang, Thomas H. Wassink, Kirsty Wing, Kerstin Wittemeyer, Shawn Wood, Brian L. Yaspan, Danielle Zurawiecki, Lonnie Zwaigenbaum, Catalina Betancur, Joseph D. Buxbaum, Rita M. Cantor, Edwin H. Cook, Hilary Coon, Michael L. Cuccaro, Louise Gallagher, Daniel H. Geschwind, Michael Gill, Jonathan L. Haines, Judith Miller, Anthony P. Monaco, John I. Nurnberger, Andrew D. Paterson, Margaret A. Pericak-Vance, Gerard D. Schellenberg, Stephen W. Scherer, James S. Sutcliffe, Peter Szatmari, Astrid M. Vicente, Veronica J. Vieland, Ellen M. Wijsman, Bernie Devlin, Sean Ennis, Joachim Hallmayer

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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 x 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 x 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.

Original language	English
Article number	ddq307
Pages (from-to)	4072 - 4082
Number of pages	11
Journal	Human Molecular Genetics
Volume	19
Issue number	20
DOIs	https://doi.org/10.1093/hmg/ddq307
Publication status	Published - 27 Jul 2010

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10.1093/hmg/ddq307

A genome-wide scan for common alleles affecting risk for autism
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Anney, R., Klei, L., Pinto, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., Sykes, N., Pagnamenta, A. T., Almeida, J., Bacchelli, E., Bailey, A. J., Baird, G., Battaglia, A., Berney, T., Bolshakova, N., Boelte, S., Bolton, P. F., ... Hallmayer, J. (2010). A genome-wide scan for common alleles affecting risk for autism. Human Molecular Genetics, 19(20), 4072 - 4082. Article ddq307. https://doi.org/10.1093/hmg/ddq307

@article{fc8d7adb5be2453f8fe16bccf61c0ba7,

title = "A genome-wide scan for common alleles affecting risk for autism",

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 x 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 x 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 = "Richard Anney and Lambertus Klei and Dalila Pinto and Regina Regan and Judith Conroy and Magalhaes, {Tiago R.} and Catarina Correia and Abrahams, {Brett S.} and Nuala Sykes and Pagnamenta, {Alistair T.} and Joana Almeida and Elena Bacchelli and Bailey, {Anthony J.} and Gillian Baird and Agatino Battaglia and Tom Berney and Nadia Bolshakova and Sven Boelte and Bolton, {Patrick F.} and Thomas Bourgeron and Sean Brennan and Jessica Brian and Carson, {Andrew R.} and Guillermo Casallo and Jillian Casey and Chu, {Su H.} and Lynne Cochrane and Christina Corsello and Crawford, {Emily L.} and Andrew Crossett and Geraldine Dawson and {de Jonge}, Maretha and Richard Delorme and Irene Drmic and Eftichia Duketis and Frederico Duque and Annette Estes and Penny Farrar and Fernandez, {Bridget A.} and Folstein, {Susan E.} and Eric Fombonne and Freitag, {Christine M.} and John Gilbert and Christopher Gillberg and Glessner, {Joseph T.} and Jeremy Goldberg and Jonathan Green and Guter, {Stephen J.} and Hakon Hakonarson and Heron, {Elizabeth A.} and Matthew Hill and Richard Holt and Howe, {Jennifer L.} and Gillian Hughes and Vanessa Hus and Roberta Igliozzi and Cecilia Kim and Klauck, {Sabine M.} and Alexander Kolevzon and Olena Korvatska and Vlad Kustanovich and Lajonchere, {Clara M.} and Lamb, {Janine A.} and Magdalena Laskawiec and Marion Leboyer and {Le Couteur}, Ann and Leventhal, {Bennett L.} and Lionel, {Anath C.} and Xiao-Qing Liu and Catherine Lord and Linda Lotspeich and Lund, {Sabata C.} and Elena Maestrini and William Mahoney and Carine Mantoulan and Marshall, {Christian R.} and Helen McConachie and McDougle, {Christopher J.} and Jane McGrath and McMahon, {William M.} and Melhem, {Nadine M.} and Alison Merikangas and Ohsuke Migita and Minshew, {Nancy J.} and Mirza, {Ghazala K.} and Jeff Munson and Nelson, {Stanley F.} and Carolyn Noakes and Abdul Noor and Gudrun Nygren and Guiomar Oliveira and Katerina Papanikolaou and Parr, {Jeremy R.} and Barbara Parrini and Tara Paton and Andrew Pickles and Joseph Piven and osey, {David J.} and Annemarie Poustka and Fritz Poustka and Aparna Prasad and Jiannis Ragoussis and Katy Renshaw and Jessica Rickaby and Wendy Roberts and Kathryn Roeder and Bernadette Roge and Rutter, {Michael L.} and Bierut, {Laura J.} and Rice, {John P.} and Jeff Salt and Katherine Sansom and Daisuke Sato and Ricardo Segurado and Lili Senman and Naisha Shah and Sheffield, {Val C.} and Latha Soorya and Ines Sousa and Vera Stoppioni and Christina Strawbridge and Raffaella Tancredi and Katherine Tansey and Bhooma Thiruvahindrapduram and Thompson, {Ann P.} and Susanne Thomson and Ana Tryfon and John Tsiantis and {Van Engeland}, Herman and Vincent, {John B.} and Fred Volkmar and Simon Wallace and Kai Wang and Zhouzhi Wang and Wassink, {Thomas H.} and Kirsty Wing and Kerstin Wittemeyer and Shawn Wood and Yaspan, {Brian L.} and Danielle Zurawiecki and Lonnie Zwaigenbaum and Catalina Betancur and Buxbaum, {Joseph D.} and Cantor, {Rita M.} and Cook, {Edwin H.} and Hilary Coon and Cuccaro, {Michael L.} and Louise Gallagher and Geschwind, {Daniel H.} and Michael Gill and Haines, {Jonathan L.} and Judith Miller and Monaco, {Anthony P.} and Nurnberger, {John I.} and Paterson, {Andrew D.} and Pericak-Vance, {Margaret A.} and Schellenberg, {Gerard D.} and Scherer, {Stephen W.} and Sutcliffe, {James S.} and Peter Szatmari and Vicente, {Astrid M.} and Vieland, {Veronica J.} and Wijsman, {Ellen M.} and Bernie Devlin and Sean Ennis and Joachim Hallmayer",

year = "2010",

month = jul,

day = "27",

doi = "10.1093/hmg/ddq307",

language = "English",

volume = "19",

pages = "4072 -- 4082",

journal = "Human Molecular Genetics",

issn = "1460-2083",

publisher = "Oxford University Press",

number = "20",

}

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, Boelte, 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, X-Q, 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, osey, DJ, Poustka, A, Poustka, F, Prasad, A, Ragoussis, J, Renshaw, K, Rickaby, J, Roberts, W, Roeder, K, Roge, B, Rutter, ML, Bierut, LJ, Rice, JP, Salt, J, Sansom, K, Sato, D, Segurado, R, Senman, L, Shah, N, Sheffield, VC, Soorya, L, Sousa, I, Stoppioni, V, Strawbridge, C, Tancredi, R, Tansey, K, Thiruvahindrapduram, B, Thompson, AP, Thomson, S, Tryfon, A, Tsiantis, J, Van Engeland, H, Vincent, JB, Volkmar, F, Wallace, S, Wang, K, Wang, Z, Wassink, TH, Wing, K, Wittemeyer, K, Wood, S, Yaspan, BL, Zurawiecki, D, Zwaigenbaum, L, Betancur, C, Buxbaum, JD, Cantor, RM, Cook, EH, Coon, H, Cuccaro, ML, Gallagher, L, Geschwind, DH, Gill, M, Haines, JL, Miller, J, Monaco, AP, Nurnberger, JI, Paterson, AD, Pericak-Vance, MA, Schellenberg, GD, Scherer, SW, Sutcliffe, JS, Szatmari, P, Vicente, AM, Vieland, VJ, Wijsman, EM, Devlin, B, Ennis, S & Hallmayer, J 2010, 'A genome-wide scan for common alleles affecting risk for autism', Human Molecular Genetics, vol. 19, no. 20, ddq307, pp. 4072 - 4082. https://doi.org/10.1093/hmg/ddq307

TY - JOUR

T1 - A genome-wide scan for common alleles affecting risk for autism

AU - Anney, Richard

AU - Klei, Lambertus

AU - Pinto, Dalila

AU - Regan, Regina

AU - Conroy, Judith

AU - Magalhaes, Tiago R.

AU - Correia, Catarina

AU - Abrahams, Brett S.

AU - Sykes, Nuala

AU - Pagnamenta, Alistair T.

AU - Almeida, Joana

AU - Bacchelli, Elena

AU - Bailey, Anthony J.

AU - Baird, Gillian

AU - Battaglia, Agatino

AU - Berney, Tom

AU - Bolshakova, Nadia

AU - Boelte, Sven

AU - Bolton, Patrick F.

AU - Bourgeron, Thomas

AU - Brennan, Sean

AU - Brian, Jessica

AU - Carson, Andrew R.

AU - Casallo, Guillermo

AU - Casey, Jillian

AU - Chu, Su H.

AU - Cochrane, Lynne

AU - Corsello, Christina

AU - Crawford, Emily L.

AU - Crossett, Andrew

AU - Dawson, Geraldine

AU - de Jonge, Maretha

AU - Delorme, Richard

AU - Drmic, Irene

AU - Duketis, Eftichia

AU - Duque, Frederico

AU - Estes, Annette

AU - Farrar, Penny

AU - Fernandez, Bridget A.

AU - Folstein, Susan E.

AU - Fombonne, Eric

AU - Freitag, Christine M.

AU - Gilbert, John

AU - Gillberg, Christopher

AU - Glessner, Joseph T.

AU - Goldberg, Jeremy

AU - Green, Jonathan

AU - Guter, Stephen J.

AU - Hakonarson, Hakon

AU - Heron, Elizabeth A.

AU - Hill, Matthew

AU - Holt, Richard

AU - Howe, Jennifer L.

AU - Hughes, Gillian

AU - Hus, Vanessa

AU - Igliozzi, Roberta

AU - Kim, Cecilia

AU - Klauck, Sabine M.

AU - Kolevzon, Alexander

AU - Korvatska, Olena

AU - Kustanovich, Vlad

AU - Lajonchere, Clara M.

AU - Lamb, Janine A.

AU - Laskawiec, Magdalena

AU - Leboyer, Marion

AU - Le Couteur, Ann

AU - Leventhal, Bennett L.

AU - Lionel, Anath C.

AU - Liu, Xiao-Qing

AU - Lord, Catherine

AU - Lotspeich, Linda

AU - Lund, Sabata C.

AU - Maestrini, Elena

AU - Mahoney, William

AU - Mantoulan, Carine

AU - Marshall, Christian R.

AU - McConachie, Helen

AU - McDougle, Christopher J.

AU - McGrath, Jane

AU - McMahon, William M.

AU - Melhem, Nadine M.

AU - Merikangas, Alison

AU - Migita, Ohsuke

AU - Minshew, Nancy J.

AU - Mirza, Ghazala K.

AU - Munson, Jeff

AU - Nelson, Stanley F.

AU - Noakes, Carolyn

AU - Noor, Abdul

AU - Nygren, Gudrun

AU - Oliveira, Guiomar

AU - Papanikolaou, Katerina

AU - Parr, Jeremy R.

AU - Parrini, Barbara

AU - Paton, Tara

AU - Pickles, Andrew

AU - Piven, Joseph

AU - osey, David J.

AU - Poustka, Annemarie

AU - Poustka, Fritz

AU - Prasad, Aparna

AU - Ragoussis, Jiannis

AU - Renshaw, Katy

AU - Rickaby, Jessica

AU - Roberts, Wendy

AU - Roeder, Kathryn

AU - Roge, Bernadette

AU - Rutter, Michael L.

AU - Bierut, Laura J.

AU - Rice, John P.

AU - Salt, Jeff

AU - Sansom, Katherine

AU - Sato, Daisuke

AU - Segurado, Ricardo

AU - Senman, Lili

AU - Shah, Naisha

AU - Sheffield, Val C.

AU - Soorya, Latha

AU - Sousa, Ines

AU - Stoppioni, Vera

AU - Strawbridge, Christina

AU - Tancredi, Raffaella

AU - Tansey, Katherine

AU - Thiruvahindrapduram, Bhooma

AU - Thompson, Ann P.

AU - Thomson, Susanne

AU - Tryfon, Ana

AU - Tsiantis, John

AU - Van Engeland, Herman

AU - Vincent, John B.

AU - Volkmar, Fred

AU - Wallace, Simon

AU - Wang, Kai

AU - Wang, Zhouzhi

AU - Wassink, Thomas H.

AU - Wing, Kirsty

AU - Wittemeyer, Kerstin

AU - Wood, Shawn

AU - Yaspan, Brian L.

AU - Zurawiecki, Danielle

AU - Zwaigenbaum, Lonnie

AU - Betancur, Catalina

AU - Buxbaum, Joseph D.

AU - Cantor, Rita M.

AU - Cook, Edwin H.

AU - Coon, Hilary

AU - Cuccaro, Michael L.

AU - Gallagher, Louise

AU - Geschwind, Daniel H.

AU - Gill, Michael

AU - Haines, Jonathan L.

AU - Miller, Judith

AU - Monaco, Anthony P.

AU - Nurnberger, John I.

AU - Paterson, Andrew D.

AU - Pericak-Vance, Margaret A.

AU - Schellenberg, Gerard D.

AU - Scherer, Stephen W.

AU - Sutcliffe, James S.

AU - Szatmari, Peter

AU - Vicente, Astrid M.

AU - Vieland, Veronica J.

AU - Wijsman, Ellen M.

AU - Devlin, Bernie

AU - Ennis, Sean

AU - Hallmayer, Joachim

PY - 2010/7/27

Y1 - 2010/7/27

N2 - 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 x 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 x 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.

AB - 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 x 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 x 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.

U2 - 10.1093/hmg/ddq307

DO - 10.1093/hmg/ddq307

M3 - Article

SN - 1460-2083

VL - 19

SP - 4072

EP - 4082

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 20

M1 - ddq307

ER -

A genome-wide scan for common alleles affecting risk for autism

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