Ερευνητικό υλικό ΕΚΠΑ

Individual common variants exert weak effects on the risk for autism
spectrum disorderspi

Αγγλικά

While it is apparent that rare variation can play an important role in
the genetic architecture of autism spectrum disorders (ASDs), the
contribution of common variation to the risk of developing ASD is less
clear. To produce a more comprehensive picture, we report Stage 2 of the
Autism Genome Project genome-wide association study, adding 1301 ASD
families and bringing the total to 2705 families analysed (Stages 1 and
2). In addition to evaluating the association of individual single
nucleotide polymorphisms (SNPs), we also sought evidence that common
variants, en masse, might affect the risk. Despite genotyping over a
million SNPs covering the genome, no single SNP shows significant
association with ASD or selected phenotypes at a genome-wide level. The
SNP that achieves the smallest P-value from secondary analyses is
rs1718101. It falls in CNTNAP2, a gene previously implicated in
susceptibility for ASD. This SNP also shows modest association with age
of word/phrase acquisition in ASD subjects, of interest because features
of language development are also associated with other variation in
CNTNAP2. In contrast, allele scores derived from the transmission of
common alleles to Stage 1 cases significantly predict case status in the
independent Stage 2 sample. Despite being significant, the variance
explained by these allele scores was small (Vm 1). Based on results from
individual SNPs and their en masse effect on risk, as inferred from the
allele score results, it is reasonable to conclude that common variants
affect the risk for ASD but their individual effects are modest.

2012

Anney, Richard
Klei, Lambertus
Pinto, Dalila
Almeida, Joana
and Bacchelli, Elena
Baird, Gillian
Bolshakova, Nadia and
Boelte, Sven
Bolton, Patrick F.
Bourgeron, Thomas
Brennan,
Sean
Brian, Jessica
Casey, Jillian
Conroy, Judith and
Correia, Catarina
Corsello, Christina
Crawford, Emily L.
de
Jonge, Maretha
Delorme, Richard
Duketis, Eftichia
Duque,
Frederico
Estes, Annette
Farrar, Penny
Fernandez, Bridget A.
and Folstein, Susan E.
Fombonne, Eric
Gilbert, John and
Gillberg, Christopher
Glessner, Joseph T.
Green, Andrew and
Green, Jonathan
Guter, Stephen J.
Heron, Elizabeth A.
Holt,
Richard
Howe, Jennifer L.
Hughes, Gillian
Hus, Vanessa and
Igliozzi, Roberta
Jacob, Suma
Kenny, Graham P.
Kim, Cecilia
and Kolevzon, Alexander
Kustanovich, Vlad
Lajonchere, Clara M.
and Lamb, Janine A.
Law-Smith, Miriam
Leboyer, Marion
Le
Couteur, Ann
Leventhal, Bennett L.
Liu, Xiao-Qing
Lombard,
Frances
Lord, Catherine
Lotspeich, Linda
Lund, Sabata C. and
Magalhaes, Tiago R.
Mantoulan, Carine
McDougle, Christopher J.
and Melhem, Nadine M.
Merikangas, Alison
Minshew, Nancy J. and
Mirza, Ghazala K.
Munson, Jeff
Noakes, Carolyn
Nygren,
Gudrun
Papanikolaou, Katerina
Pagnamenta, Alistair T. and
Parrini, Barbara
Paton, Tara
Pickles, Andrew
Posey, David J.
and Poustka, Fritz
Ragoussis, Jiannis
Regan, Regina
Roberts,
Wendy
Roeder, Kathryn
Roge, Bernadette
Rutter, Michael L.
and Schlitt, Sabine
Shah, Naisha
Sheffield, Val C.
Soorya,
Latha
Sousa, Ines
Stoppioni, Vera
Sykes, Nuala
Tancredi,
Raffaella
Thompson, Ann P.
Thomson, Susanne
Tryfon, Ana and
Tsiantis, John
Van Engeland, Herman
Vincent, John B. and
Volkmar, Fred
Vorstman, J. A. S.
Wallace, Simon
Wing, Kirsty
and Wittemeyer, Kerstin
Wood, Shawn
Zurawiecki, Danielle and
Zwaigenbaum, Lonnie
Bailey, Anthony J.
Battaglia, Agatino and
Cantor, Rita M.
Coon, Hilary
Cuccaro, Michael L.
Dawson,
Geraldine
Ennis, Sean
Freitag, Christine M.
Geschwind,
Daniel H.
Haines, Jonathan L.
Klauck, Sabine M.
McMahon,
William M.
Maestrini, Elena
Miller, Judith
Monaco, Anthony
P.
Nelson, Stanley F.
Nurnberger, Jr., John I.
Oliveira,
Guiomar
Parr, Jeremy R.
Pericak-Vance, Margaret A.
Piven,
Joseph
Schellenberg, Gerard D.
Scherer, StephenW.
Vicente,
Astrid M.
Wassink, Thomas H.
Wijsman, Ellen M.
Betancur,
Catalina
Buxbaum, Joseph D.
Cook, Edwin H.
Gallagher, Louise
and Gill, Michael
Hallmayer, Joachim
Paterson, Andrew D. and
Sutcliffe, James S.
Szatmari, Peter
Vieland, Veronica J. and
Hakonarson, Hakon
Devlin, Bernie

Human Molecular Genetics

Oxford University Press

21

21

4781-4792

https://doi.org/10.1093/hmg/dds301

10.1093/hmg/dds301

https://pergamos.lib.uoa.gr/uoa/dl/object/3154362