TY - JOUR
T1 - A genomewide screen for autism susceptibility loci
AU - Autism Genetic Resource Exchange Consortium
AU - Liu, Jianjun
AU - Nyholt, Dale R.
AU - Magnussen, Patrick
AU - Parano, Enrico
AU - Pavone, Piero
AU - Geschwind, Daniel
AU - Lord, Catherine
AU - Iversen, Portia
AU - Hoh, Josephine
AU - Ott, Jurg
AU - Gilliam, T. Conrad
AU - Bucan, Maya M.
AU - Brown, W. Ted
AU - Buxbaum, Joseph J.
AU - Cook, Edwin H.
AU - Gilliam, T. Conrad
AU - Greenberg, David A.
AU - Ledbetter, David H.
AU - Miller, Bruce B.
AU - Nelson, Stanley F.
AU - Pevsner, Jonathan
AU - Rotter, Jerome I.
AU - Schellenberg, Gerard D.
AU - Sprouse, Carol A.
AU - Tanzi, Rudolph E.
AU - Wilhelmsen, Kirk C.
AU - Silverman, Jeremy M.
N1 - Funding Information:
We thank Cure Autism Now (CAN), the Autism Genetic Resource Exchange (AGRE), and Dr. Judith P. Sulzberger, for support (to J.L. and T.C.G.) for this research. We also gratefully acknowledge support (to E.P. and P.P.) from Telethon, Italy (grant E.911). We thank Adina Grun, Xiaomei Tong, and Miguel Brito, for technical support. Most importantly, we thank the families who have participated in and contributed to these studies.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - We report the analysis of 335 microsatellite markers genotyped in 110 multiplex families with autism. All families include at least two "affected" siblings, at least one of whom has autism; the remaining affected sibs carry diagnoses of either Asperger syndrome or pervasive developmental disorder. Affected sib-pair analysis yielded multipoint maximum LOD scores (MLS) that reach the accepted threshold for suggestive linkage on chromosomes 5, X, and 19. Nominal evidence for linkage (point-wise P <. 05) was obtained on chromosomes 2, 3, 4, 8, 10, 11, 12, 15, 16, 18, and 20, and secondary loci were found on chromosomes 5 and 19. Analysis of families sharing alleles at the putative X chromosomal linked locus and one or more other putative linked loci produced an MLS of 3.56 for the DXS470-D19S174 marker combination. In an effort to increase power to detect linkage, scan statistics were used to evaluate the significance of peak LOD scores based on statistical evidence at adjacent marker loci. This analysis yielded impressive evidence for linkage to autism and autism-spectrum disorders with significant genome-wide P values <.05 for markers on chromosomes 5 and 8 and with suggestive linkage evidence for a marker on chromosome 19.
AB - We report the analysis of 335 microsatellite markers genotyped in 110 multiplex families with autism. All families include at least two "affected" siblings, at least one of whom has autism; the remaining affected sibs carry diagnoses of either Asperger syndrome or pervasive developmental disorder. Affected sib-pair analysis yielded multipoint maximum LOD scores (MLS) that reach the accepted threshold for suggestive linkage on chromosomes 5, X, and 19. Nominal evidence for linkage (point-wise P <. 05) was obtained on chromosomes 2, 3, 4, 8, 10, 11, 12, 15, 16, 18, and 20, and secondary loci were found on chromosomes 5 and 19. Analysis of families sharing alleles at the putative X chromosomal linked locus and one or more other putative linked loci produced an MLS of 3.56 for the DXS470-D19S174 marker combination. In an effort to increase power to detect linkage, scan statistics were used to evaluate the significance of peak LOD scores based on statistical evidence at adjacent marker loci. This analysis yielded impressive evidence for linkage to autism and autism-spectrum disorders with significant genome-wide P values <.05 for markers on chromosomes 5 and 8 and with suggestive linkage evidence for a marker on chromosome 19.
UR - http://www.scopus.com/inward/record.url?scp=0034920299&partnerID=8YFLogxK
U2 - 10.1086/321980
DO - 10.1086/321980
M3 - Article
C2 - 11452361
AN - SCOPUS:0034920299
SN - 0002-9297
VL - 69
SP - 327
EP - 340
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -