Characterizing features of the genetic architecture underlying autism from a multi-ancestry perspective.

Authors

Marla Mendes, Chen Yang Xu, Worrawat Engchuan, Brett Trost, Xiaopu Zhou, Bruno Akio Miwa, Nelson Bautista Salazar, Jack Iglar, Bhooma Thiruvahindrapuram, Liam Wallich, Thales Henrique de Paiva, Eduardo Tarazona-Santos, Bridget Fernandez, Victor Borda, Stephen W Scherer

Published in

Molecular psychiatry. Sep 11, 2026. Epub Sep 11, 2026.

Abstract

Autism spectrum disorder (ASD; MIM 209850) is reported to vary globally from 0.01% in East Asian populations to 4.36% in certain Australian cohorts. Despite high heritability estimates (61-94%), the genetic architecture underlying ASD susceptibility remains poorly characterized across diverse populations, as most genomic studies have initially focused on individuals of European ancestry. To investigate ancestry-specific genetic contributions to ASD, we analyzed whole-genome sequencing data from three independent ASD cohorts. We identified admixed ASD probands (n = 1 033) and ancestry-matched controls (n = 1 033) and performed admixture mapping (AM). AM using five continental reference populations (European, African, East Asian, South Asian, and Native American) identified five ancestry-specific ASD-susceptibility loci, including one African-related locus at 1p21.2 near S1PR1 and four Native American-associated loci at chromosome 11q13.4. Three of these latter loci were contiguous and encompassed genes previously implicated in ASD, notably SHANK2 and DHCR7, with fine-mapping identifying a significantly associated variant between the two genes (rs77695321; P = 1.52 × 10⁻⁷). The fourth Native American-associated signal at 11q13.4 overlapped the folate receptor genes FOLR1 and FOLR3, with fine-mapping identifying a genome-wide significant variant (rs7950807; P = 5.21 × 10⁻⁸). A secondary admixture mapping analysis restricted to Latin American individuals, incorporating 6 487 Brazilian controls, identified 16 additional ancestry-specific loci across seven genomic regions.

PMID:
42728317
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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