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Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism

Author

Listed:
  • Yiqin Wang

    (Cornell University)

  • Xiaoxian Guo

    (Cornell University)

  • Xiumei Hong

    (Johns Hopkins University Bloomberg School of Public Health)

  • Guoying Wang

    (Johns Hopkins University Bloomberg School of Public Health)

  • Colleen Pearson

    (Boston University School of Medicine and Boston Medical Center)

  • Barry Zuckerman

    (Boston University School of Medicine and Boston Medical Center)

  • Andrew G. Clark

    (Cornell University
    Cornell University)

  • Kimberly O. O’Brien

    (Cornell University)

  • Xiaobin Wang

    (Johns Hopkins University Bloomberg School of Public Health
    Johns Hopkins University School of Medicine)

  • Zhenglong Gu

    (Cornell University
    Fudan University)

Abstract

Mitochondria are essential for brain development. While previous studies linked dysfunctional mitochondria with autism spectrum disorder (ASD), the role of the mitochondrial genome (mtDNA) in ASD risk is largely unexplored. This study investigates the association of mtDNA heteroplasmies (co-existence of mutated and unmutated mtDNA) and content with ASD, as well as its inter-generational transmission and sex differences among two independent samples: a family-based study (n = 1,938 families with parents, probands and sibling controls) and a prospective birth cohort (n = 997 mother-child pairs). In both samples, predicted pathogenic (PP) heteroplasmies in children are associated with ASD risk (Meta-OR = 1.56, P = 0.00068). Inter-generational transmission of mtDNA reveals attenuated effects of purifying selection on maternal heteroplasmies in children with ASD relative to controls, particularly among males. Among children with ASD and PP heteroplasmies, increased mtDNA content shows benefits for cognition, communication, and behaviors (P ≤ 0.02). These results underscore the value of exploring maternal and newborn mtDNA in ASD.

Suggested Citation

  • Yiqin Wang & Xiaoxian Guo & Xiumei Hong & Guoying Wang & Colleen Pearson & Barry Zuckerman & Andrew G. Clark & Kimberly O. O’Brien & Xiaobin Wang & Zhenglong Gu, 2022. "Association of mitochondrial DNA content, heteroplasmies and inter-generational transmission with autism," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30805-7
    DOI: 10.1038/s41467-022-30805-7
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    1. Sharon Ben-Hur & Shoshana Sernik & Sara Afar & Alina Kolpakova & Yoav Politi & Liron Gal & Anat Florentin & Ofra Golani & Ehud Sivan & Nili Dezorella & David Morgenstern & Shmuel Pietrokovski & Eyal S, 2024. "Egg multivesicular bodies elicit an LC3-associated phagocytosis-like pathway to degrade paternal mitochondria after fertilization," Nature Communications, Nature, vol. 15(1), pages 1-25, December.

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