TY - JOUR
T1 - The female protective effect in autism spectrum disorder is not mediated by a single genetic locus Dr Meng-Chuan Lai
AU - Gockley, Jake
AU - Willsey, A. Jeremy
AU - Dong, Shan
AU - Dougherty, Joseph D.
AU - Constantino, John N.
AU - Sanders, Stephan J.
N1 - Publisher Copyright:
© 2015 Gockley et al.; licensee BioMed Central.
PY - 2015/5/13
Y1 - 2015/5/13
N2 - Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis. Methods: To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. Results: No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect. Conclusions: The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE.
AB - Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis. Methods: To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. Results: No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect. Conclusions: The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE.
KW - Autism spectrum disorder
KW - Female protective effect
KW - GWAS
KW - Sex bias
UR - http://www.scopus.com/inward/record.url?scp=85027920405&partnerID=8YFLogxK
U2 - 10.1186/s13229-015-0014-3
DO - 10.1186/s13229-015-0014-3
M3 - Article
AN - SCOPUS:85027920405
SN - 2040-2392
VL - 6
JO - Molecular Autism
JF - Molecular Autism
IS - 1
M1 - 6
ER -