TY  - JOUR
A1  - Casey, Jillian P.
A1  - Magalhães, Tiago R.
A1  - Conroy, Judith M.
A1  - Regan, Regina
A1  - Shah, Naisha
A1  - Anney, Richard
A1  - Shields, Denis C.
A1  - Abrahams, Brett S.
A1  - Almeida, Joana
A1  - Bacchelli, Elena
A1  - Bailey, Anthony J.
A1  - Baird, Gillian
A1  - Battaglia, Agatino
A1  - Berney, Tom
A1  - Bolshakova, Nadia
A1  - Bolton, Patrick F.
A1  - Bourgeron, Thomas
A1  - Brennan, Sean
A1  - Cali, Phil
A1  - Correia, Catarina
A1  - Corsello, Christina
A1  - Coutanche, Marc
A1  - Dawson, Geraldine
A1  - Jonge, Maretha de
A1  - Delorme, Richard
A1  - Duketis, Eftichia
A1  - Duque, Frederico
A1  - Estes, Annette
A1  - Farrar, Penny
A1  - Fernandez, Bridget A.
A1  - Folstein, Susan E.
A1  - Foley, Suzanne
A1  - Fombonne, Eric
A1  - Freitag, Christine M.
A1  - Gilbert, John
A1  - Gillberg, Christopher
A1  - Glessner, Joseph T.
A1  - Green, Jonathan
A1  - Guter, Stephen J.
A1  - Hakonarson, Hakon
A1  - Holt, Richard
A1  - Hughes, Gillian
A1  - Hus, Vanessa
A1  - Igliozzi, Roberta
A1  - Kim, Cecilia
A1  - Klauck, Sabine M.
A1  - Kolevzon, Alexander
A1  - Lamb, Janine A.
A1  - Leboyer, Marion
A1  - Le Couteur, Ann
A1  - Leventhal, Bennett L.
A1  - Lord, Catherine
A1  - Lund, Sabata C.
A1  - Maestrini, Elena
A1  - Mantoulan, Carine
A1  - Marshall, Christian R.
A1  - McConachie, Helen
A1  - McDougle, Christopher J.
A1  - McGrath, Jane
A1  - McMahon, William M.
A1  - Merikangas, Alison
A1  - Miller, Judith
A1  - Minopoli, Fiorella
A1  - Mirza, Ghazala K.
A1  - Munson, Jeff
A1  - Nelson, Stanley F.
A1  - Nygren, Gudrun
A1  - Oliveira, Guiomar
A1  - Pagnamenta, Alistair T.
A1  - Papanikolaou, Katerina
A1  - Parr, Jeremy R.
A1  - Parrini, Barbara
A1  - Pickles, Andrew
A1  - Pinto, Dalila
A1  - Piven, Joseph
A1  - Posey, David J.
A1  - Poustka, Annemarie
A1  - Poustka, Fritz
A1  - Ragoussis, Jiannis
A1  - Roge, Bernadette
A1  - Rutter, Michael L.
A1  - Sequeira, Ana F.
A1  - Soorya, Latha
A1  - Sousa, Inês
A1  - Sykes, Nuala
A1  - Stoppioni, Vera
A1  - Tancredi, Raffaella
A1  - Tauber, Maïté
A1  - Thompson, Ann P.
A1  - Thomson, Susanne
A1  - Tsiantis, John
A1  - Engeland, Herman van
A1  - Vincent, John B.
A1  - Volkmar, Fred
A1  - Vorstman, Jacob A. S.
A1  - Wallace, Simon
A1  - Wang, Kai
A1  - Wassink, Thomas H.
A1  - White, Kathy
A1  - Wing, Kirsty
A1  - Wittemeyer, Kerstin
A1  - Yaspan, Brian L.
A1  - Zwaigenbaum, Lonnie
A1  - Betancur, Catalina
A1  - Buxbaum, Joseph D.
A1  - Cantor, Rita M.
A1  - Cook, Edwin H.
A1  - Coon, Hilary
A1  - Cuccaro, Michael L.
A1  - Geschwind, Daniel H.
A1  - Haines, Jonathan L.
A1  - Hallmayer, Joachim
A1  - Monaco, Anthony P.
A1  - Nurnberger, John I.
A1  - Pericak-Vance, Margaret Ann
A1  - Schellenberg, Gerard D.
A1  - Scherer, Stephen W.
A1  - Sutcliffe, James S.
A1  - Szatmari, Peter
A1  - Vieland, Veronica J.
A1  - Wijsman, Ellen M.
A1  - Green, Andrew
A1  - Gill, Michael
A1  - Gallagher, Louise
A1  - Vicente, Astrid M.
A1  - Ennis, Sean
T1  - A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder
T2  - Human Genetics
N2  - Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/30006
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-300063
SN  - 0340-6717
SN  - 1432-1203
N1  - Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
N1  - Electronic supplementary material The online version of this article (doi:10.1007/s00439-011-1094-6) contains supplementary material, which is available to authorized users.
VL  - 131
SP  - 565
EP  - 579
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -