A genome-wide scan for common alleles affecting risk for autism.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Anney
Richard
R
Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Ireland.
Klei
Lambertus
L
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Dalila
D
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Regina
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Judith
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TR
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AT
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E
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AJ
Baird
Gillian
G
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Agatino
A
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Nadia
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PF
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AR
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Jillian
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SH
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C
Crawford
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de Jonge
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Drmic
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Duketis
Eftichia
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F
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BA
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CM
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EA
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JL
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G
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A
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JA
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Jiannis
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Katy
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Kathryn
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Bernadette
B
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Michael L
ML
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Laura J
LJ
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JP
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Katherine
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Daisuke
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Ricardo
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Lili
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Shah
Naisha
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Sheffield
Val C
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Soorya
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Inês
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Stoppioni
Vera
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Strawbridge
Christina
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Tancredi
Raffaella
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Tansey
Katherine
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Thiruvahindrapduram
Bhooma
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Ann P
AP
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Susanne
S
Tryfon
Ana
A
Tsiantis
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J
Van Engeland
Herman
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John B
JB
Volkmar
Fred
F
Wallace
Simon
S
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Kai
K
Wang
Zhouzhi
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Wassink
Thomas H
TH
Wing
Kirsty
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Wittemeyer
Kerstin
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BL
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RM
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Edwin H
EH
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H
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ML
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Daniel H
DH
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JL
Miller
Judith
J
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AP
Nurnberger
John I
JI
Paterson
Andrew D
AD
Pericak-Vance
Margaret A
MA
Schellenberg
Gerard D
GD
Scherer
Stephen W
SW
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JS
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P
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Astrid M
AM
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D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics