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 journalArticlepeer-review

494 Scopus citations


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 languageEnglish (US)
Pages (from-to)802-808
Number of pages7
Issue number7265
StatePublished - Oct 8 2009
Externally publishedYes

ASJC Scopus subject areas

  • General


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