TY - JOUR
T1 - Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity
AU - Buxbaum, Joseph D.
AU - Silverman, Jeremy M.
AU - Smith, Christopher J.
AU - Kilifarski, Mario
AU - Reichert, Jennifer
AU - Hollander, Eric
AU - Lawlor, Brian A.
AU - Fitzgerald, Michael
AU - Greenberg, David A.
AU - Davis, Kenneth L.
N1 - Funding Information:
We thank Dr. Susan Hodge for insights into the use of the predivided sample test. We also thank Cure Autism Now and the Autism Genetic Resource Exchange for providing DNA samples. These studies were supported by grants from the Seaver Autism Research Center (to K.L.D.) and Cure Autism Now (to J.D.B.).
PY - 2001
Y1 - 2001
N2 - Although there is considerable evidence for a strong genetic component to idiopathic autism, several genomewide screens for susceptibility genes have been performed with limited concordance of linked loci, reflecting either numerous genes of weak effect and/or sample heterogeneity. Because decreasing sample heterogeneity would increase the power to identify genes, the effect on evidence for linkage of restricting a sample of autism-affected relative pairs to those with delayed onset (at age >36 mo) of phrase speech (PSD, for phrase speech delay) was studied. In the second stage of a two-stage genome screen for susceptibility loci involving 95 families with two or more individuals with autism or related disorders, a maximal multipoint heterogeneity LOD score (HLOD) of 1.96 and a maximal multipoint nonparametric linkage (NPL) score of 2.39 was seen on chromosome 2q. Restricting the analysis to the subset of families (n = 49) with two or more individuals having a narrow diagnosis of autism and PSD generated a maximal multipoint HLOD score of 2.99 and an NPL score of 3.32. The increased scores in the restricted sample, together with evidence for heterogeneity in the entire sample, indicate that the restricted sample comprises a population that is more genetically homogeneous, which could therefore increase the likelihood of positional cloning of susceptibility loci.
AB - Although there is considerable evidence for a strong genetic component to idiopathic autism, several genomewide screens for susceptibility genes have been performed with limited concordance of linked loci, reflecting either numerous genes of weak effect and/or sample heterogeneity. Because decreasing sample heterogeneity would increase the power to identify genes, the effect on evidence for linkage of restricting a sample of autism-affected relative pairs to those with delayed onset (at age >36 mo) of phrase speech (PSD, for phrase speech delay) was studied. In the second stage of a two-stage genome screen for susceptibility loci involving 95 families with two or more individuals with autism or related disorders, a maximal multipoint heterogeneity LOD score (HLOD) of 1.96 and a maximal multipoint nonparametric linkage (NPL) score of 2.39 was seen on chromosome 2q. Restricting the analysis to the subset of families (n = 49) with two or more individuals having a narrow diagnosis of autism and PSD generated a maximal multipoint HLOD score of 2.99 and an NPL score of 3.32. The increased scores in the restricted sample, together with evidence for heterogeneity in the entire sample, indicate that the restricted sample comprises a population that is more genetically homogeneous, which could therefore increase the likelihood of positional cloning of susceptibility loci.
UR - http://www.scopus.com/inward/record.url?scp=0034982149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034982149&partnerID=8YFLogxK
U2 - 10.1086/320588
DO - 10.1086/320588
M3 - Article
C2 - 11353400
AN - SCOPUS:0034982149
SN - 0002-9297
VL - 68
SP - 1514
EP - 1520
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -