Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Szatmari
Peter
P
Paterson
Andrew D
AD
Zwaigenbaum
Lonnie
L
Roberts
Wendy
W
Brian
Jessica
J
Liu
Xiao-Qing
XQ
Vincent
John B
JB
Skaug
Jennifer L
JL
Thompson
Ann P
AP
Senman
Lili
L
Feuk
Lars
L
Qian
Cheng
C
Bryson
Susan E
SE
Jones
Marshall B
MB
Marshall
Christian R
CR
Scherer
Stephen W
SW
Vieland
Veronica J
VJ
Bartlett
Christopher
C
Mangin
La Vonne
LV
Goedken
Rhinda
R
Segre
Alberto
A
Pericak-Vance
Margaret A
MA
Cuccaro
Michael L
ML
Gilbert
John R
JR
Wright
Harry H
HH
Abramson
Ruth K
RK
Betancur
Catalina
C
Bourgeron
Thomas
T
Gillberg
Christopher
C
Leboyer
Marion
M
Buxbaum
Joseph D
JD
Davis
Kenneth L
KL
Hollander
Eric
E
Silverman
Jeremy M
JM
Hallmayer
Joachim
J
Lotspeich
Linda
L
Sutcliffe
James S
JS
Haines
Jonathan L
JL
Folstein
Susan E
SE
Piven
Joseph
J
Wassink
Thomas H
TH
Sheffield
Val
V
Geschwind
Daniel H
DH
Bucan
Maja
M
Brown
W Ted
WT
Cantor
Rita M
RM
Constantino
John N
JN
Gilliam
T Conrad
TC
Herbert
Martha
M
Lajonchere
Clara
C
Ledbetter
David H
DH
Lese-Martin
Christa
C
Miller
Janet
J
Nelson
Stan
S
Samango-Sprouse
Carol A
CA
Spence
Sarah
S
State
Matthew
M
Tanzi
Rudolph E
RE
Coon
Hilary
H
Dawson
Geraldine
G
Devlin
Bernie
B
Estes
Annette
A
Flodman
Pamela
P
Klei
Lambertus
L
McMahon
William M
WM
Minshew
Nancy
N
Munson
Jeff
J
Korvatska
Elena
E
Rodier
Patricia M
PM
Schellenberg
Gerard D
GD
Smith
Moyra
M
Spence
M Anne
MA
Stodgell
Chris
C
Tepper
Ping Guo
PG
Wijsman
Ellen M
EM
Yu
Chang-En
CE
Rogé
Bernadette
B
Mantoulan
Carine
C
Wittemeyer
Kerstin
K
Poustka
Annemarie
A
Felder
Bärbel
B
Klauck
Sabine M
SM
Schuster
Claudia
C
Poustka
Fritz
F
Bölte
Sven
S
Feineis-Matthews
Sabine
S
Herbrecht
Evelyn
E
Schmötzer
Gabi
G
Tsiantis
John
J
Papanikolaou
Katerina
K
Maestrini
Elena
E
Bacchelli
Elena
E
Blasi
Francesca
F
Carone
Simona
S
Toma
Claudio
C
Van Engeland
Herman
H
de Jonge
Maretha
M
Kemner
Chantal
C
Koop
Frederieke
F
Koop
Frederike
F
Langemeijer
Marjolein
M
Langemeijer
Marjolijn
M
Hijmans
Channa
C
Hijimans
Channa
C
Staal
Wouter G
WG
Baird
Gillian
G
Bolton
Patrick F
PF
Rutter
Michael L
ML
Weisblatt
Emma
E
Green
Jonathan
J
Aldred
Catherine
C
Wilkinson
Julie-Anne
JA
Pickles
Andrew
A
Le Couteur
Ann
A
Berney
Tom
T
McConachie
Helen
H
Bailey
Anthony J
AJ
Francis
Kostas
K
Honeyman
Gemma
G
Hutchinson
Aislinn
A
Parr
Jeremy R
JR
Wallace
Simon
S
Monaco
Anthony P
AP
Barnby
Gabrielle
G
Kobayashi
Kazuhiro
K
Lamb
Janine A
JA
Sousa
Ines
I
Sykes
Nuala
N
Cook
Edwin H
EH
Guter
Stephen J
SJ
Leventhal
Bennett L
BL
Salt
Jeff
J
Lord
Catherine
C
Corsello
Christina
C
Hus
Vanessa
V
Weeks
Daniel E
DE
Volkmar
Fred
F
Tauber
Maïté
M
Fombonne
Eric
E
Shih
Andy
A
Meyer
Kacie J
KJ
D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D008126:Lod Score; D008297:Male; D012307:Risk Factors