Pleiotropic Mechanisms Indicated for Sex Differences in Autism

Ileena Mitra, Kathryn Tsang, Christine Ladd-Acosta, Lisa A. Croen, Kimberly A. Aldinger, Robert L. Hendren, Michela Traglia, Alinoë Lavillaureix, Noah Zaitlen, Michael C. Oldham, Pat Levitt, Stanley Nelson, David G Amaral, Irva Herz-Picciotto, M. Daniele Fallin, Lauren A. Weiss

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Sexual dimorphism in common disease is pervasive, including a dramatic male preponderance in autism spectrum disorders (ASDs). Potential genetic explanations include a liability threshold model requiring increased polymorphism risk in females, sex-limited X-chromosome contribution, gene-environment interaction driven by differences in hormonal milieu, risk influenced by genes sex-differentially expressed in early brain development, or contribution from general mechanisms of sexual dimorphism shared with secondary sex characteristics. Utilizing a large single nucleotide polymorphism (SNP) dataset, we identify distinct sex-specific genome-wide significant loci. We investigate genetic hypotheses and find no evidence for increased genetic risk load in females, but evidence for sex heterogeneity on the X chromosome, and contribution of sex-heterogeneous SNPs for anthropometric traits to ASD risk. Thus, our results support pleiotropy between secondary sex characteristic determination and ASDs, providing a biological basis for sex differences in ASDs and implicating non brain-limited mechanisms.

Original languageEnglish (US)
Article numbere1006425
JournalPLoS Genetics
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2016

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Autistic Disorder
gender differences
Sex Characteristics
gender
sexual dimorphism
brain
chromosome
polymorphism
Single Nucleotide Polymorphism
pleiotropy
Genetic Load
X chromosome
gene
liability
Gene-Environment Interaction
X-Linked Genes
Brain
X Chromosome
genome
genotype-environment interaction

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Mitra, I., Tsang, K., Ladd-Acosta, C., Croen, L. A., Aldinger, K. A., Hendren, R. L., ... Weiss, L. A. (2016). Pleiotropic Mechanisms Indicated for Sex Differences in Autism. PLoS Genetics, 12(11), [e1006425]. https://doi.org/10.1371/journal.pgen.1006425

Pleiotropic Mechanisms Indicated for Sex Differences in Autism. / Mitra, Ileena; Tsang, Kathryn; Ladd-Acosta, Christine; Croen, Lisa A.; Aldinger, Kimberly A.; Hendren, Robert L.; Traglia, Michela; Lavillaureix, Alinoë; Zaitlen, Noah; Oldham, Michael C.; Levitt, Pat; Nelson, Stanley; Amaral, David G; Herz-Picciotto, Irva; Fallin, M. Daniele; Weiss, Lauren A.

In: PLoS Genetics, Vol. 12, No. 11, e1006425, 01.11.2016.

Research output: Contribution to journalArticle

Mitra, I, Tsang, K, Ladd-Acosta, C, Croen, LA, Aldinger, KA, Hendren, RL, Traglia, M, Lavillaureix, A, Zaitlen, N, Oldham, MC, Levitt, P, Nelson, S, Amaral, DG, Herz-Picciotto, I, Fallin, MD & Weiss, LA 2016, 'Pleiotropic Mechanisms Indicated for Sex Differences in Autism', PLoS Genetics, vol. 12, no. 11, e1006425. https://doi.org/10.1371/journal.pgen.1006425
Mitra I, Tsang K, Ladd-Acosta C, Croen LA, Aldinger KA, Hendren RL et al. Pleiotropic Mechanisms Indicated for Sex Differences in Autism. PLoS Genetics. 2016 Nov 1;12(11). e1006425. https://doi.org/10.1371/journal.pgen.1006425
Mitra, Ileena ; Tsang, Kathryn ; Ladd-Acosta, Christine ; Croen, Lisa A. ; Aldinger, Kimberly A. ; Hendren, Robert L. ; Traglia, Michela ; Lavillaureix, Alinoë ; Zaitlen, Noah ; Oldham, Michael C. ; Levitt, Pat ; Nelson, Stanley ; Amaral, David G ; Herz-Picciotto, Irva ; Fallin, M. Daniele ; Weiss, Lauren A. / Pleiotropic Mechanisms Indicated for Sex Differences in Autism. In: PLoS Genetics. 2016 ; Vol. 12, No. 11.
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