{
  "abstract": "Autism Spectrum Disorder (ASD) arises from complex genetic and environmental factors, with inherited genetic variation playing a substantial role. This study introduces a novel approach to uncover moderate effect size (MES) genes in ASD, which individually do not meet the ASD liability threshold but collectively contribute when paired with specific other MES genes. Analyzing 10,795 families from the SPARK dataset, we identified 97 MES genes forming 50 significant gene pairs, demonstrating a substantial association with ASD when considered in tandem, but not individually. Our method leverages familial inheritance patterns and statistical analyses, refined by comparisons against control cohorts, to elucidate these gene pairs' contribution to ASD liability. Furthermore, expression profile analyses of these genes in brain tissues underscore their relevance to ASD pathology. This study underscores the complexity of ASD's genetic landscape, suggesting that gene combinations, beyond high impact single-gene mutations, significantly contribute to the disorder's etiology and heterogeneity. Our findings pave the way for new avenues in understanding ASD's genetic underpinnings and developing targeted therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Icahn School of Medicine at Mount Sinai",
    "Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Broad Institute of MIT and Harvard",
    "Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA",
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. behrang.mahjani@mssm.edu",
    "Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. behrang.mahjani@mssm.edu",
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. behrang.mahjani@mssm.edu",
    "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. behrang.mahjani@mssm.edu",
    "Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. behrang.mahjani@mssm.edu",
    "Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA. behrang.mahjani@mssm.edu",
    "Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. behrang.mahjani@mssm.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Madison Caballero",
      "orcid": "0000-0002-4499-5105"
    },
    {
      "affs": [
        2,
        3,
        4,
        5
      ],
      "name": "F. Kyle Satterstrom",
      "orcid": "0000-0001-6187-7680"
    },
    {
      "affs": [
        6,
        7,
        8,
        0,
        1
      ],
      "name": "Silvia de Rubeis",
      "orcid": "0000-0001-9383-6883"
    },
    {
      "affs": [
        6,
        7,
        9,
        8,
        0,
        10,
        1
      ],
      "name": "Joseph D. Buxbaum",
      "orcid": "0000-0001-8898-8313"
    },
    {
      "affs": [
        11,
        12,
        13,
        14,
        15,
        16,
        17
      ],
      "name": "Behrang Mahjani",
      "orcid": "0000-0001-6087-9537"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/22zp8qytrr112.bib",
  "cited_by": 5,
  "doi": "10.1038/s42003-026-10380-z",
  "fulltext_url": null,
  "id": "22zp8qytrr112",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://doi.org/10.1038/s42003-026-10380-z",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2805|Autism Spectrum Disorder Research"
    ]
  ],
  "openalex": "W4393942106",
  "pdf_url": null,
  "pmcid": "PMC11023658",
  "pmid": "38633780",
  "published": "2026-05-30",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/22zp8qytrr112.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:53Z",
      "native_id": "W4393942106",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s42003-026-10380-z"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2805|Autism Spectrum Disorder Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Identification of moderate effect size genes in autism spectrum disorder through a novel gene pairing approach",
  "title_text": "Identification of moderate effect size genes in autism spectrum disorder through a novel gene pairing approach",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/22zp8qytrr112",
  "venue": "Communications Biology",
  "versions": []
}