A genome-wide linkage and association scan reveals novel loci for autism

Lauren A. Weiss; Dan E. Arking; Mark J. Daly; Aravinda Chakravarti; Camille W. Brune; Kristen West; Ashley O'Connor; Gina Hilton; Rebecca L. Tomlinson; Andrew B. West; Edwin H. Cook; Todd Green; Shun Chiao Chang; Stacey Gabriel; Casey Gates; Ellen M. Hanson; Andrew Kirby; Joshua Korn; Finny Kuruvilla; Steven McCarroll; Eric M. Morrow; Benjamin Neale; Shaun Purcell; Roksana Sasanfar; Carrie Sougnez; Christine Stevens; David Altshuler; James Gusella; Susan L. Santangelo; Pamela Sklar; Rudolph Tanzi; Richard Anney; Anthony J. Bailey; Gillian Baird; Agatino Battaglia; Tom Berney; Catalina Betancur; Sven Bölte; Patrick F. Bolton; Jessica Brian; Susan E. Bryson; Joseph D. Buxbaum; Ines Cabrito; Guiqing Cai; Rita M. Cantor; Hilary Coon; Judith Conroy; Catarina Correia; Christina Corsello; Emily L. Crawford; Michael L. Cuccaro; Geraldine Dawson; Maretha De Jonge; Bernie Devlin; Eftichia Duketis; Sean Ennis; Annette Estes; Penny Farrar; Eric Fombonne; Christine M. Freitag; Louise Gallagher; Daniel H. Geschwind; John Gilbert; Michael Gill; Christopher Gillberg; Jeremy Goldberg; Andrew Green; Jonathan Green; Stephen J. Guter; Jonathan L. Haines; Joachim F. Hallmayer; Vanessa Hus; Sabine M. Klauck; Olena Korvatska; Janine A. Lamb; Magdalena Laskawiec; Marion Leboyer; Ann Le Couteur; Bennett L. Leventha; Xiao Qing Liu; Catherine Lord; Linda J. Lotspeich; Elena Maestrini; Tiago Magalhaes; William Mahoney; Carine Mantoulan; Helen McConachie; Christopher J. McDougle; William M. McMahon; Christian R. Marshall; Judith Miller; Nancy J. Minshew; Anthony P. Monaco; Jeff Munson; John I. Nurnberger; Guiomar Oliveira; Alistair Pagnamenta; Katerina Papanikolaou; Jeremy R. Parr; Andrew D. Paterson; Margaret A. Pericak-Vance; Andrew Pickles; Dalila Pinto; Joseph Piven; David J. Posey; Annemarie Poustka; Fritz Poustka; Regina Regan; Jennifer Reichert; Katy Renshaw; Wendy Roberts; Bernadette Roge; Michael L. Rutter; Jeff Salt; Gerard D. Schellenberg; Stephen W. Scherer; Val Sheffield; James S. Sutcliffe; Peter Szatmari; Katherine Tansey; Ann P. Thompson; John Tsiantis; Herman Van Engeland; Astrid M. Vicente; Veronica J. Vieland; Fred Volkmar; Simon Wallace; Thomas H. Wassink; Ellen M. Wijsman; Kirsty Wing; Kerstin Wittemeyer; Brian L. Yaspan; Lonnie Zwaigenbaum; Seung Yun Yoo; Robert Sean Hill; Nahit M. Mukaddes; Soher Balkhy; Generoso Gascon; Samira Al-Saad; Asif Hashmi; Janice Ware; Robert M. Joseph; Elaine LeClair; Jennifer N. Partlow; Brenda Barry; Christopher A. Walsh; David Pauls; Irma Moilanen; Hanna Ebeling; Marja Leena Mattila; Sanna Kuusikko; Katja Jussila; Jaakko Ignatius; Ala Tolouei; Majid Ghadami; Maryam Rostami; Azam Hosseinipour; Maryam Valujerdi; Kara Andresen; Brian Winkloski; Stephen Haddad; Lou Kunkel; Zak Kohane; Tram Tran; Sek Won Kong; Stephanie Brewster O'Neil; Rachel Hundley; Ingrid Holm; Heather Peters; Elizabeth Baroni; Aislyn Cangialose; Lindsay Jackson; Lisa Albers; Ronald Becker; Carolyn Bridgemohan; Sandra Friedman; Kerim Munir; Ramzi Nazir; Judith Palfrey; Alison Schonwald; Esau Simmons; Leonard A. Rappaport; Julie Gauthier; Laurent Mottron; Ridha Joober; Guy Rouleau; Karola Rehnstrom; Lennart Von Wendt; Leena Peltonen

doi:10.1038/nature08490

A genome-wide linkage and association scan reveals novel loci for autism

Lauren A. Weiss, Dan E. Arking, Mark J. Daly, Aravinda Chakravarti, Camille W. Brune, Kristen West, Ashley O'Connor, Gina Hilton, Rebecca L. Tomlinson, Andrew B. West, Edwin H. Cook, Todd Green, Shun Chiao Chang, Stacey Gabriel, Casey Gates, Ellen M. Hanson, Andrew Kirby, Joshua Korn, Finny Kuruvilla, Steven McCarrollEric M. Morrow, Benjamin Neale, Shaun Purcell, Roksana Sasanfar, Carrie Sougnez, Christine Stevens, David Altshuler, James Gusella, Susan L. Santangelo, Pamela Sklar, Rudolph Tanzi, Richard Anney, Anthony J. Bailey, Gillian Baird, Agatino Battaglia, Tom Berney, Catalina Betancur, Sven Bölte, Patrick F. Bolton, Jessica Brian, Susan E. Bryson, Joseph D. Buxbaum, Ines Cabrito, Guiqing Cai, Rita M. Cantor, Hilary Coon, Judith Conroy, Catarina Correia, Christina Corsello, Emily L. Crawford, Michael L. Cuccaro, Geraldine Dawson, Maretha De Jonge, Bernie Devlin, Eftichia Duketis, Sean Ennis, Annette Estes, Penny Farrar, Eric Fombonne, Christine M. Freitag, Louise Gallagher, Daniel H. Geschwind, John Gilbert, Michael Gill, Christopher Gillberg, Jeremy Goldberg, Andrew Green, Jonathan Green, Stephen J. Guter, Jonathan L. Haines, Joachim F. Hallmayer, Vanessa Hus, Sabine M. Klauck, Olena Korvatska, Janine A. Lamb, Magdalena Laskawiec, Marion Leboyer, Ann Le Couteur, Bennett L. Leventha, Xiao Qing Liu, Catherine Lord, Linda J. Lotspeich, Elena Maestrini, Tiago Magalhaes, William Mahoney, Carine Mantoulan, Helen McConachie, Christopher J. McDougle, William M. McMahon, Christian R. Marshall, Judith Miller, Nancy J. Minshew, Anthony P. Monaco, Jeff Munson, John I. Nurnberger, Guiomar Oliveira, Alistair Pagnamenta, Katerina Papanikolaou, Jeremy R. Parr, Andrew D. Paterson, Margaret A. Pericak-Vance, Andrew Pickles, Dalila Pinto, Joseph Piven, David J. Posey, Annemarie Poustka, Fritz Poustka, Regina Regan, Jennifer Reichert, Katy Renshaw, Wendy Roberts, Bernadette Roge, Michael L. Rutter, Jeff Salt, Gerard D. Schellenberg, Stephen W. Scherer, Val Sheffield, James S. Sutcliffe, Peter Szatmari, Katherine Tansey, Ann P. Thompson, John Tsiantis, Herman Van Engeland, Astrid M. Vicente, Veronica J. Vieland, Fred Volkmar, Simon Wallace, Thomas H. Wassink, Ellen M. Wijsman, Kirsty Wing, Kerstin Wittemeyer, Brian L. Yaspan, Lonnie Zwaigenbaum, Seung Yun Yoo, Robert Sean Hill, Nahit M. Mukaddes, Soher Balkhy, Generoso Gascon, Samira Al-Saad, Asif Hashmi, Janice Ware, Robert M. Joseph, Elaine LeClair, Jennifer N. Partlow, Brenda Barry, Christopher A. Walsh, David Pauls, Irma Moilanen, Hanna Ebeling, Marja Leena Mattila, Sanna Kuusikko, Katja Jussila, Jaakko Ignatius, Ala Tolouei, Majid Ghadami, Maryam Rostami, Azam Hosseinipour, Maryam Valujerdi, Kara Andresen, Brian Winkloski, Stephen Haddad, Lou Kunkel, Zak Kohane, Tram Tran, Sek Won Kong, Stephanie Brewster O'Neil, Rachel Hundley, Ingrid Holm, Heather Peters, Elizabeth Baroni, Aislyn Cangialose, Lindsay Jackson, Lisa Albers, Ronald Becker, Carolyn Bridgemohan, Sandra Friedman, Kerim Munir, Ramzi Nazir, Judith Palfrey, Alison Schonwald, Esau Simmons, Leonard A. Rappaport, Julie Gauthier, Laurent Mottron, Ridha Joober, Guy Rouleau, Karola Rehnstrom, Lennart Von Wendt, Leena Peltonen

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

Abstract

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 × 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.

Original language	English
Pages (from-to)	802-808
Number of pages	6
Journal	Nature
Volume	461
Issue number	7265
DOIs	https://doi.org/10.1038/nature08490
Publication status	Published - 8 Oct 2009

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10.1038/nature08490

Cite this

Weiss, L. A., Arking, D. E., Daly, M. J., Chakravarti, A., Brune, C. W., West, K., O'Connor, A., Hilton, G., Tomlinson, R. L., West, A. B., Cook, E. H., Green, T., Chang, S. C., Gabriel, S., Gates, C., Hanson, E. M., Kirby, A., Korn, J., Kuruvilla, F., ... Peltonen, L. (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461(7265), 802-808. https://doi.org/10.1038/nature08490

@article{9dd8b634c6f8435cbf91eb25d25ab41a,

title = "A genome-wide linkage and association scan reveals novel loci for autism",

abstract = "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 × 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.",

author = "Weiss, {Lauren A.} and Arking, {Dan E.} and Daly, {Mark J.} and Aravinda Chakravarti and Brune, {Camille W.} and Kristen West and Ashley O'Connor and Gina Hilton and Tomlinson, {Rebecca L.} and West, {Andrew B.} and Cook, {Edwin H.} and Todd Green and Chang, {Shun Chiao} and Stacey Gabriel and Casey Gates and Hanson, {Ellen M.} and Andrew Kirby and Joshua Korn and Finny Kuruvilla and Steven McCarroll and Morrow, {Eric M.} and Benjamin Neale and Shaun Purcell and Roksana Sasanfar and Carrie Sougnez and Christine Stevens and David Altshuler and James Gusella and Santangelo, {Susan L.} and Pamela Sklar and Rudolph Tanzi and Richard Anney and Bailey, {Anthony J.} and Gillian Baird and Agatino Battaglia and Tom Berney and Catalina Betancur and Sven B{\"o}lte and Bolton, {Patrick F.} and Jessica Brian and Bryson, {Susan E.} and Buxbaum, {Joseph D.} and Ines Cabrito and Guiqing Cai and Cantor, {Rita M.} and Hilary Coon and Judith Conroy and Catarina Correia and Christina Corsello and Crawford, {Emily L.} and Cuccaro, {Michael L.} and Geraldine Dawson and {De Jonge}, Maretha and Bernie Devlin and Eftichia Duketis and Sean Ennis and Annette Estes and Penny Farrar and Eric Fombonne and Freitag, {Christine M.} and Louise Gallagher and Geschwind, {Daniel H.} and John Gilbert and Michael Gill and Christopher Gillberg and Jeremy Goldberg and Andrew Green and Jonathan Green and Guter, {Stephen J.} and Haines, {Jonathan L.} and Hallmayer, {Joachim F.} and Vanessa Hus and Klauck, {Sabine M.} and Olena Korvatska and Lamb, {Janine A.} and Magdalena Laskawiec and Marion Leboyer and {Le Couteur}, Ann and Leventha, {Bennett L.} and Liu, {Xiao Qing} and Catherine Lord and Lotspeich, {Linda J.} and Elena Maestrini and Tiago Magalhaes and William Mahoney and Carine Mantoulan and Helen McConachie and McDougle, {Christopher J.} and McMahon, {William M.} and Marshall, {Christian R.} and Judith Miller and Minshew, {Nancy J.} and Monaco, {Anthony P.} and Jeff Munson and Nurnberger, {John I.} and Guiomar Oliveira and Alistair Pagnamenta and Katerina Papanikolaou and Parr, {Jeremy R.} and Paterson, {Andrew D.} and Pericak-Vance, {Margaret A.} and Andrew Pickles and Dalila Pinto and Joseph Piven and Posey, {David J.} and Annemarie Poustka and Fritz Poustka and Regina Regan and Jennifer Reichert and Katy Renshaw and Wendy Roberts and Bernadette Roge and Rutter, {Michael L.} and Jeff Salt and Schellenberg, {Gerard D.} and Scherer, {Stephen W.} and Val Sheffield and Sutcliffe, {James S.} and Peter Szatmari and Katherine Tansey and Thompson, {Ann P.} and John Tsiantis and {Van Engeland}, Herman and Vicente, {Astrid M.} and Vieland, {Veronica J.} and Fred Volkmar and Simon Wallace and Wassink, {Thomas H.} and Wijsman, {Ellen M.} and Kirsty Wing and Kerstin Wittemeyer and Yaspan, {Brian L.} and Lonnie Zwaigenbaum and Yoo, {Seung Yun} and Hill, {Robert Sean} and Mukaddes, {Nahit M.} and Soher Balkhy and Generoso Gascon and Samira Al-Saad and Asif Hashmi and Janice Ware and Joseph, {Robert M.} and Elaine LeClair and Partlow, {Jennifer N.} and Brenda Barry and Walsh, {Christopher A.} and David Pauls and Irma Moilanen and Hanna Ebeling and Mattila, {Marja Leena} and Sanna Kuusikko and Katja Jussila and Jaakko Ignatius and Ala Tolouei and Majid Ghadami and Maryam Rostami and Azam Hosseinipour and Maryam Valujerdi and Kara Andresen and Brian Winkloski and Stephen Haddad and Lou Kunkel and Zak Kohane and Tram Tran and {Won Kong}, Sek and O'Neil, {Stephanie Brewster} and Rachel Hundley and Ingrid Holm and Heather Peters and Elizabeth Baroni and Aislyn Cangialose and Lindsay Jackson and Lisa Albers and Ronald Becker and Carolyn Bridgemohan and Sandra Friedman and Kerim Munir and Ramzi Nazir and Judith Palfrey and Alison Schonwald and Esau Simmons and Rappaport, {Leonard A.} and Julie Gauthier and Laurent Mottron and Ridha Joober and Guy Rouleau and Karola Rehnstrom and {Von Wendt}, Lennart and Leena Peltonen",

year = "2009",

month = oct,

day = "8",

doi = "10.1038/nature08490",

language = "English",

volume = "461",

pages = "802--808",

journal = "Nature",

issn = "0028-0836",

publisher = "Springer Nature",

number = "7265",

}

Weiss, LA, Arking, DE, Daly, MJ, Chakravarti, A, Brune, CW, West, K, O'Connor, A, Hilton, G, Tomlinson, RL, West, AB, Cook, EH, 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, 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, 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, Le Couteur, A, Leventha, 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, 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, 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, Tolouei, A, Ghadami, M, Rostami, M, Hosseinipour, A, Valujerdi, M, Andresen, K, Winkloski, B, Haddad, S, Kunkel, L, Kohane, Z, Tran, T, Won Kong, S, O'Neil, SB, 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, Rouleau, G, Rehnstrom, K, Von Wendt, L & Peltonen, L 2009, 'A genome-wide linkage and association scan reveals novel loci for autism', Nature, vol. 461, no. 7265, pp. 802-808. https://doi.org/10.1038/nature08490

TY - JOUR

T1 - A genome-wide linkage and association scan reveals novel loci for autism

AU - Weiss, Lauren A.

AU - Arking, Dan E.

AU - Daly, Mark J.

AU - Chakravarti, Aravinda

AU - Brune, Camille W.

AU - West, Kristen

AU - O'Connor, Ashley

AU - Hilton, Gina

AU - Tomlinson, Rebecca L.

AU - West, Andrew B.

AU - Cook, Edwin H.

AU - Green, Todd

AU - Chang, Shun Chiao

AU - Gabriel, Stacey

AU - Gates, Casey

AU - Hanson, Ellen M.

AU - Kirby, Andrew

AU - Korn, Joshua

AU - Kuruvilla, Finny

AU - McCarroll, Steven

AU - Morrow, Eric M.

AU - Neale, Benjamin

AU - Purcell, Shaun

AU - Sasanfar, Roksana

AU - Sougnez, Carrie

AU - Stevens, Christine

AU - Altshuler, David

AU - Gusella, James

AU - Santangelo, Susan L.

AU - Sklar, Pamela

AU - Tanzi, Rudolph

AU - Anney, Richard

AU - Bailey, Anthony J.

AU - Baird, Gillian

AU - Battaglia, Agatino

AU - Berney, Tom

AU - Betancur, Catalina

AU - Bölte, Sven

AU - Bolton, Patrick F.

AU - Brian, Jessica

AU - Bryson, Susan E.

AU - Buxbaum, Joseph D.

AU - Cabrito, Ines

AU - Cai, Guiqing

AU - Cantor, Rita M.

AU - Coon, Hilary

AU - Conroy, Judith

AU - Correia, Catarina

AU - Corsello, Christina

AU - Crawford, Emily L.

AU - Cuccaro, Michael L.

AU - Dawson, Geraldine

AU - De Jonge, Maretha

AU - Devlin, Bernie

AU - Duketis, Eftichia

AU - Ennis, Sean

AU - Estes, Annette

AU - Farrar, Penny

AU - Fombonne, Eric

AU - Freitag, Christine M.

AU - Gallagher, Louise

AU - Geschwind, Daniel H.

AU - Gilbert, John

AU - Gill, Michael

AU - Gillberg, Christopher

AU - Goldberg, Jeremy

AU - Green, Andrew

AU - Green, Jonathan

AU - Guter, Stephen J.

AU - Haines, Jonathan L.

AU - Hallmayer, Joachim F.

AU - Hus, Vanessa

AU - Klauck, Sabine M.

AU - Korvatska, Olena

AU - Lamb, Janine A.

AU - Laskawiec, Magdalena

AU - Leboyer, Marion

AU - Le Couteur, Ann

AU - Leventha, Bennett L.

AU - Liu, Xiao Qing

AU - Lord, Catherine

AU - Lotspeich, Linda J.

AU - Maestrini, Elena

AU - Magalhaes, Tiago

AU - Mahoney, William

AU - Mantoulan, Carine

AU - McConachie, Helen

AU - McDougle, Christopher J.

AU - McMahon, William M.

AU - Marshall, Christian R.

AU - Miller, Judith

AU - Minshew, Nancy J.

AU - Monaco, Anthony P.

AU - Munson, Jeff

AU - Nurnberger, John I.

AU - Oliveira, Guiomar

AU - Pagnamenta, Alistair

AU - Papanikolaou, Katerina

AU - Parr, Jeremy R.

AU - Paterson, Andrew D.

AU - Pericak-Vance, Margaret A.

AU - Pickles, Andrew

AU - Pinto, Dalila

AU - Piven, Joseph

AU - Posey, David J.

AU - Poustka, Annemarie

AU - Poustka, Fritz

AU - Regan, Regina

AU - Reichert, Jennifer

AU - Renshaw, Katy

AU - Roberts, Wendy

AU - Roge, Bernadette

AU - Rutter, Michael L.

AU - Salt, Jeff

AU - Schellenberg, Gerard D.

AU - Scherer, Stephen W.

AU - Sheffield, Val

AU - Sutcliffe, James S.

AU - Szatmari, Peter

AU - Tansey, Katherine

AU - Thompson, Ann P.

AU - Tsiantis, John

AU - Van Engeland, Herman

AU - Vicente, Astrid M.

AU - Vieland, Veronica J.

AU - Volkmar, Fred

AU - Wallace, Simon

AU - Wassink, Thomas H.

AU - Wijsman, Ellen M.

AU - Wing, Kirsty

AU - Wittemeyer, Kerstin

AU - Yaspan, Brian L.

AU - Zwaigenbaum, Lonnie

AU - Yoo, Seung Yun

AU - Hill, Robert Sean

AU - Mukaddes, Nahit M.

AU - Balkhy, Soher

AU - Gascon, Generoso

AU - Al-Saad, Samira

AU - Hashmi, Asif

AU - Ware, Janice

AU - Joseph, Robert M.

AU - LeClair, Elaine

AU - Partlow, Jennifer N.

AU - Barry, Brenda

AU - Walsh, Christopher A.

AU - Pauls, David

AU - Moilanen, Irma

AU - Ebeling, Hanna

AU - Mattila, Marja Leena

AU - Kuusikko, Sanna

AU - Jussila, Katja

AU - Ignatius, Jaakko

AU - Tolouei, Ala

AU - Ghadami, Majid

AU - Rostami, Maryam

AU - Hosseinipour, Azam

AU - Valujerdi, Maryam

AU - Andresen, Kara

AU - Winkloski, Brian

AU - Haddad, Stephen

AU - Kunkel, Lou

AU - Kohane, Zak

AU - Tran, Tram

AU - Won Kong, Sek

AU - O'Neil, Stephanie Brewster

AU - Hundley, Rachel

AU - Holm, Ingrid

AU - Peters, Heather

AU - Baroni, Elizabeth

AU - Cangialose, Aislyn

AU - Jackson, Lindsay

AU - Albers, Lisa

AU - Becker, Ronald

AU - Bridgemohan, Carolyn

AU - Friedman, Sandra

AU - Munir, Kerim

AU - Nazir, Ramzi

AU - Palfrey, Judith

AU - Schonwald, Alison

AU - Simmons, Esau

AU - Rappaport, Leonard A.

AU - Gauthier, Julie

AU - Mottron, Laurent

AU - Joober, Ridha

AU - Rouleau, Guy

AU - Rehnstrom, Karola

AU - Von Wendt, Lennart

AU - Peltonen, Leena

PY - 2009/10/8

Y1 - 2009/10/8

N2 - 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 × 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.

AB - 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 × 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.

U2 - 10.1038/nature08490

DO - 10.1038/nature08490

M3 - Article

C2 - 19812673

SN - 0028-0836

VL - 461

SP - 802

EP - 808

JO - Nature

JF - Nature

IS - 7265

ER -

A genome-wide linkage and association scan reveals novel loci for autism

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