Evidence for parent-of-origin effects in autism spectrum disorder: a narrative review

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Abstract

Autism spectrum disorder (ASD) is a heterogeneous group of early-onset neurodevelopmental disorders known to be highly heritable with a complex genetic architecture. Abnormal brain developmental trajectories that impact synaptic functioning, excitation-inhibition balance and brain connectivity are now understood to play a central role in ASD. Ongoing efforts to identify the genetic underpinnings still prove challenging, in part due to phenotypic and genetic heterogeneity.

This review focuses on parent-of-origin effects (POEs), where the phenotypic effect of an allele depends on its parental origin. POEs include genomic imprinting, transgenerational effects, mitochondrial DNA, sex chromosomes and mutational transmission bias. The motivation for investigating these mechanisms in ASD has been driven by their known impacts on early brain development and brain functioning, in particular for the most well-documented POE, genomic imprinting. Moreover, imprinting is implicated in syndromes such as Angelman and Prader-Willi, which frequently share comorbid symptoms with ASD. In addition to other regions in the genome, this comprehensive review highlights the 15q11-q13 and 7q chromosomal regions as well as the mitochondrial DNA as harbouring the majority of currently identified POEs in ASD.

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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Yuan-Pang Wang, Maheswar Satpathy, Mathilde Touvier … (2018)

Summary Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8–75·9 million [7·2%, 6·0–8·3]), 45·1 million (29·0–62·8 million [5·6%, 4·0–7·2]), 36·3 million (25·3–50·9 million [4·5%, 3·8–5·3]), 34·7 million (23·0–49·6 million [4·3%, 3·5–5·2]), and 34·1 million (23·5–46·0 million [4·2%, 3·2–5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3–3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0–11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer’s disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862–11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018–19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.

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The contribution of de novo coding mutations to autism spectrum disorder.

Ivan Iossifov, Brian J. O’Roak, Stephan Sanders … (2014)

Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.

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Nonparametric estimation of Shannon’s index of diversity when there are unseen species in sample

Catherine Lord, Susan Risi, Linda Lambrecht … (2000)

Journal of Autism and Developmental Disorders, 30(3), 205-223

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Author and article information

Contributors

Elizabeth A. Heron:

ORCID: http://orcid.org/0000-0003-2219-4005

eaheron@tcd.ie

Journal

Journal ID (nlm-ta): J Appl Genet

Journal ID (iso-abbrev): J Appl Genet

Title: Journal of Applied Genetics

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1234-1983

ISSN (Electronic): 2190-3883

Publication date (Electronic): 30 January 2023

Publication date PMC-release: 30 January 2023

Publication date (Print): 2023

Volume: 64

Issue: 2

Pages: 303-317

Affiliations

GRID grid.8217.c, ISNI 0000 0004 1936 9705, Neuropsychiatric Genetics Research Group, Department of Psychiatry, , Trinity College Dublin, ; Dublin, Ireland

Author notes

Communicated by Michal Witt

Author information

Niamh M. Ryan http://orcid.org/0000-0001-9773-2248

Elizabeth A. Heron http://orcid.org/0000-0003-2219-4005

Article

Publisher ID: 742

DOI: 10.1007/s13353-022-00742-8

PMC ID: 10076404

PubMed ID: 36710277

SO-VID: ea9e43e6-c474-4d76-a1d2-28f289c4efdc

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 12 September 2022

Date revision received : 8 December 2022

Date accepted : 15 December 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000874, Brain and Behavior Research Foundation;

Award ID: 24875

Award Recipient : Elizabeth A. Heron

Funded by: University of Dublin, Trinity College

Open Access :

Open Access funding provided by the IReL Consortium

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issue-copyright-statement © The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences 2023

ScienceOpen disciplines: Genetics

Keywords: autism,autism spectrum disorder,imprinting,mitochondrial dna,angelman,prader-willi

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ScienceOpen disciplines: Genetics

Keywords: autism, autism spectrum disorder, imprinting, mitochondrial dna, angelman, prader-willi

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Evidence for parent-of-origin effects in autism spectrum disorder: a narrative review

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Most cited references 142

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

The contribution of de novo coding mutations to autism spectrum disorder.

Nonparametric estimation of Shannon’s index of diversity when there are unseen species in sample

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