Parental traits may influence neurodevelopmental disorders
summary: The researchers revealed that assessing parental traits for neurodevelopmental and psychiatric disorders provides a more accurate prediction of these conditions in children than genetic testing alone. The study found that children’s risk of developing disorders such as autism and schizophrenia increases when both parents display associated traits, including depression and anxiety.
This approach outperforms traditional genetic screening by accounting for complex genetic variants passed down from parents that might otherwise go undetected. The findings, based on an analysis of 97,000 families, underscore the importance of considering both genetic and trait-based inheritance in understanding and potentially treating neurodevelopmental disorders.
- The study assessed the presence of neurodevelopmental and psychiatric traits in more than 97,000 families, revealing a higher incidence of the disorders in children whose parents showed related traits.
- This method provides a more precise understanding of the inheritance of diseases, suggesting that assortative mating based on psychological and neurodevelopmental traits can influence the severity and prevalence of these conditions in offspring.
- The research highlights the potential for using parental traits to inform genetic counseling and the development of targeted therapeutic interventions, emphasizing the need for a broader approach to predicting and managing neurodevelopmental disorders.
source: Pennsylvania state
The course of neurodevelopmental and psychiatric disorders such as autism or schizophrenia is difficult to predict, because they can be influenced by many different genetic and environmental factors.
A new study, conducted by Penn State researchers, shows that assessing parents for trait manifestations of these disorders — and related illnesses such as depression and anxiety — may provide a more accurate way to predict the prevalence and potential severity of the disorders in children. Children affected by screening for genetic variants alone.
This is likely due, at least in part, to genetic variants that parents pass on to the child that cannot be routinely picked up in genetic screening and lead to more severe disease, the researchers explained.
A paper describing the research appeared in American Journal of Human Genetics.
According to the researchers, understanding how both parents contribute to their child’s diagnosis can inform genetic counseling and the development of treatment intervention plans for children affected by these disorders.
“We investigated the presence of neurodevelopmental and psychological traits in children and parents from a wide range of families,” said Santhosh Girirajan, interim department chair and professor of biochemistry and molecular biology in the Eberly College of Science at Penn State University. Lead author of this paper.
“We have seen an increase in the presence of neurodevelopmental disorders in children whose parents report having this trait, including psychological traits such as anxiety or depression.”
The team looked at 97,000 families, many with children with neurodevelopmental disorders, such as autism or intellectual disability, and assessed the extent to which risk factors – genetic traits and the presence of traits – in both parents influenced the course of the disease in the children.
The datasets included genetic information and questionnaire data from families in a large public biobank, as well as from families from specific studies of neurodevelopmental disorders.
The researchers assessed parents and their children for symptoms of various disorders, and also evaluated known genetic mutations that can lead to such disorders. Their analysis revealed that parents tend to choose partners with the same or related disorders, leading to increased prevalence and possibly severity of the disorder in their children.
“Most neurodevelopmental disorders are genetically complex, meaning they are not caused by a single gene,” Girirajan said. “This makes it difficult to trace the exact genetic basis of the disorder in an individual, and even more difficult to predict how the disorder will develop in affected children.”
The researchers explained that complex genetic diseases can be caused by mutations in many genes, each of which can be inherited from one or both parents, or occur spontaneously in the child’s newly formed genome.
A child’s prognosis stems from the combination of mutations they inherit and how they interact with each other during development. This is called the “multiple hit model” because the disease is caused by multiple different mutations in many different genes.
“We have been studying one such mutation — a deletion of a small portion of chromosome 16 — that has been implicated as a risk factor for several neurodevelopmental disorders,” Girirajan said. Symptoms of these disorders can manifest as seizures, manifestations of schizophrenia, depression and anxiety, along with addiction-related characteristics.
“This mutation is often passed from one parent to the child, but the child regularly has more severe symptoms of the disorder than the parent. We wanted to know whether other ‘consequences’ of the disorder might come from the other parent. So, we studied the traits of both parents in a group A large number of families have children with neurodevelopmental disorders.
The research team found that the parent who went through the deletion had less severe symptoms than their child or even different but related psychological disorders such as depression or anxiety. They also found that the other parent often had similar psychological traits.
“What we realized, and what has been studied for a long time, is that there is a phenomenon called ‘assortative mating’ in humans,” said Corinne Smolin, a graduate student at Penn State who works with Girirajan and first author of the study.
“Whether consciously or unconsciously, people with similar traits prefer to find each other as partners. Although there could be other explanations, we see it in our data, and this is probably what leads to what we see in the families we studied.” .
The researchers explained that the parent who does not have the deletion must have these traits due to some other genetic mutation, and when these mutations combine with the deletion in the child’s genome, the result is a more serious disease.
By assessing traits in both parents, the researchers were able to predict the course of the disease in their children more accurately than could be achieved through genetic testing alone. They can also eventually use this information to try to identify new mutations — those inherited from parents without deletions — that are involved in causing these traits.
“We found that there is a good correlation between the traits present in the parents,” Girirajan said.
“A person with schizophrenia is more likely to find a partner with schizophrenia, and a person with anxiety and depression is more likely to find a partner with anxiety and depression. This is known by other things, like tall people marrying tall people.”
“Since all of these traits have at least some genetic components that can be similar between partners, this leads to a situation similar, but less clear, to endogamy, when people who are related through descent marry.”
In this case, trait-based assortative mating – rather than kinship – appears to lead to genetic similarity between partners which could lead to more cases and potentially more severe traits in their offspring, Girirajan explained. For example, researchers saw that when neither partner suffered from anxiety, 12.6% of their male children did.
This number jumped to 25.7% when one parent reported having anxiety and to 33.8% when both parents reported having anxiety. This increase in prevalence indicates an increase in risk because more risky traits are more likely to be identified, according to the research team.
In addition to Girirajan and Smolin, the research team includes Matthew Jensen, Lucila Piso, Anastasia Tereshkina, Dibru Banerjee, Laura Rohan, and Emily Huber at Penn State; Lisa Dyer and Jane Yosola at GeneDx, in Maryland; Laila Al Khattabi at the Paris Auxiliary Hospitals in France; Paolo Prontera at Santa Maria della Misericordia Hospital in Italy; Jean-Hubert Caberg at the University Hospital Center of Liège in Belgium; Anke van Dijk and R. Frank Koe at the University and University Hospital of Antwerp in Belgium; Charles Schwartz at the Greenwood Genetic Center in South Carolina; Laurence Pfeiffer, Patrick Callier, and Mathilde Lefebvre at the University of Bourgogne-Franche-Comté in France; Anne-Laure Mosca-Boidron at the Laboratory of Chromosomal and Molecular Genetics in France; Kate Pope, Penny Snell, and Paul J. Lockhart at the University of Melbourne in Australia; David J. matters at the Murdoch Children’s Research Institute in Australia; Lucia Castiglia, Ornella Gallese, Emanuela Avola, and Maria Grazia Brocceri at the Oasi Research Institute in Italy; Teresa Mattina, Marco Fichera, and Corrado Romano at the University of Catania in Italy; Giuseppa Maria Luana Mandara at ASP Ragusa in Italy; Olivier Pichon, Sylvester Quinat, Sandra Mercier, Claire Benneteau and Bertrand Isidore at CHU Nantes in France; Cédric Le Caignac at the University of Toulouse in France; Radka Stoeva at CHU de Le Mans in France; Sophie Plisson and Dominique Martin-Couignard at Bretonneau University Hospital in France; Ashley Nordsletten at the University of Michigan; and Eric Sistermans at UMC Amsterdam in the Netherlands.
Grants from the US National Institutes of Health, the South Carolina Department of Disabilities and Special Needs, and the Italian Department of Health Resirca Corriente supported this research.
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author: Sam Schultheis
source: Pennsylvania state
communication: Sam Schultis – Penn State
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“Assortative mating and parental genetic relatedness contribute to the pathogenesis of variable expression variants” by Santhosh Girirajan et al. American Journal of Human Genetics
Assortative mating and parental genetic relatedness contribute to the pathogenesis of variable expression variants
We screened more than 97,000 families from four UK neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents that contribute to the risk of neurodevelopmental disease in children.
We identified within- and across-disorder associations between six parent-child phenotypes, i.e., OCD (R = 0.32–0.38, p < 10).-126).
We also found that measures of subclinical autism traits in parents correlated with several measures of autism severity in children, including mean scores on the Biparental Social Responsiveness Scale and Repetitive Behaviors Scale scores (regression coefficient = 0.14, p = 3.38 × 10).-4).
We also describe patterns of phenotypic similarity between couples, with couples showing associations for six neuropsychiatric phenotypes, including the within-disorder association for depression (R = 0.24–0.68, p < 0.001) and the cross-disorder association between anxiety and bipolar disorder. perturbation (R = 0.09–0.22, p < 10-92).
Using a simulated ensemble, we also found that assortative mating can lead to increased disease susceptibility across generations and the emergence of “genetic surveillance” in families carrying rare variants. We have identified several families in the neurodevelopmental disease group where the domain inherited multiple rare variants in disease-associated genes from each affected parent.
We also identified parental relatedness as a risk factor for neurodevelopmental disorders through its inverse relationship with variable pathogenicity and proposed that parental relatedness modifies disease risk by increasing genome-wide homozygosity in children (R = 0.05–0.26, p < 0.05).
Our results highlight the utility of assessing parental phenotypes and genotypes toward trait prediction in children carrying variably expressed rare variants and point to assortative mating as a risk factor for increased disease severity in these families.