Summary: Researchers have used a novel method to examine biological connections to adolescent mental health issues by identifying associations with behaviors like monitor time and coffee consumption. The study highlights a range of possible modifiable factors that perhaps contribute to clinical risk by focusing on hereditary scores that reflect genomic predispositions.
Though causality is n’t established, these findings offer a foundation for early intervention strategies in adolescence. Despite limitations owing to ancestry representation, the study highlights the potential for genetic research to inform protective emotional health measures.
Important Information:
- Large genetic testing reveals connections between actions and mental health risk.
- Desktop time, power beverage intake, and stress-related events may relate with biological threat.
- The research emphasizes the value of creating different genetic datasets for deeper understanding.
Origin: WUSTL
Experts at Washington University in St. Louis have used the “big search” method to investigate how genetic influences affect children behavior by sifting through the data to identify all the traits, behaviors, and environments that define who we are and how they relate to hereditary relationships that account for risk for mental health problems.
Important new insights have been discovered about psychopathy biological risk, including stressful life events and display time, thanks to this cutting-edge approach. Although the findings, published in , Nature Mental Health,  , are unable to declare if one causes the other, the results provide promising prospects to understand the nature of medical problems emerging during childhood.
” We’re catching all the little fish here”, said Nicole Karcher, associate professor of psychiatry at WashU Medicine, likening their genetic testing equipment to trawling the sea.
” But now we have to sift through the bass that we caught, and coming steps should include determining how significant these are in terms of reducing the risk of mental health concerns are.”
An innovative approach to” catching” risk factors
Genome-wide Associations Studies ( GWAS ) provide a large portion of the information that we know about the connections between the genome and behavior. They link specific genetic variants across the genome with a phenotype. Phenotypes can range from physical characteristics to psychiatric disorders ( e. g., depression, anxiety ).
Some cognitive conditions are related genetically. Results from a GWAS searching for genetic links to depression, so, may also indicate biological associations with often co-occurring conditions such as stress.
We were interested in adopting a more independent, data-driven strategy to the wealth of information that is contained in large datasets because we know that one behavior varying is not going to be the only association with biological risk, said Karcher.
Doing so would maybe reveal not only expected connections between psychiatric symptoms and genetic risk, but also potential novel connections that might give more insight into how psychiatric disorder risk may develop.  ,
So senior author Karcher and first author Sarah Paul, a graduate student in Ryan Bogdan ‘s , Behavioral Research and Imaging Neurogenetics Laboratory , at Art &, Sciences,  , ran what’s called a phenome-wide association study ( PheWAS ) that inverts the GWAS.
Their PheWAS examined the relation of genetic variants known to be linked to mental health disorders and their connection to hundreds of determined variables that included behavior, symptoms, environments, health problems, and additional phenotypes rather than starting with the medical condition and looking for associated biological variants.
They included approximately 1, 300 to 1, 700 phenotypes in total from the , Adolescent Brain Cognitive Development ( ABCD ) Study.
” We took a very large approach”, said Paul, describing various phenotypes as “anything from impulse control problems and difficult behaviour or psychotic-like experiences to monitor time, to how much coffee they consumed”.
Think of it like huge online fishing.
That means they want to recognize organizations between genetic tendency and potentially modifiable risk factors that can be possible addressed , before , the emergence of psychology, Bogdan, the Dean’s Distinguished Professor of Psychological &, Brain Sciences in Arts &, Sciences, said.
What they caught
The outcomes of the PheWAS reveal some unexpected outcomes and confirm some of what they already know about the genetic risks and behaviors that are linked to youth mental health disorders.
The WashU researchers took 11 GWAS and created four broad genetic risk factors, or polygenic scores: neurodevelopmental, internalizing ( e. g., depression, anxiety ), compulsive and psychotic.
What are some of the connections they discovered in those categories:
Some 190 phenotypes, including inattention and impulsivity issues, as well as total screen time, sleep issues, and psychotic-like experiences, were linked to genetic risk for neurodevelopmental psychopathology ( predominantly ADHD and Autism Spectrum Disorder, as well as Major Depressive Disorder, Major Depressive Disorder, and problematic alcohol use ). Neurodevelopmental genetic risk is related to even more serious environmental factors, such as neighborhood crime rates and lower parental monitoring.
*Genetic risk for internalizing behavior ( Major Depressive Disorder, Generalized Anxiety Disorder, PTSD, as well as problematic alcohol use ) were broadly associated with some 120 phenotypes such as depression, stressful life events, psychotic-like experiences and screen time.
Other than less schoolwork and a higher energy consumption, there were few phenotype associations between the two psychopaths ( predominally Schizophrenia and Bipolar Disorder ).
Karcher said it was a little surprising that “genetic liability” for mental health issues may manifest in potentially modifiable behaviors in early childhood and early adolescence.
The research identified hundreds and hundreds of variables that might be linked to genetic risk, and the findings identified a number of associations, including the link between screentime and neurodevelopmental genetic risk, she continued.
She said,” The PheWAS was able to highlight these pockets of associations that may not have been otherwise discovered.”
The association between the consumption of energy drinks and the risk of psychotic disorders was one such pocket. These studies are looking at correlation, not causation, so they cannot conclude that energy drink consumption causes psychotic disorders.
These people may have genetic predisposition to psychotic disorders, and those same predispositions may also be linked to increased consuming of caffeinated beverages.
A play might have a similar effect because of the strong connection between screen time and neurodevelopmental risk.
The purpose of the PheWAS is not to sort those causation details, but to point the way with” a 20, 000-foot view of the associations,” Karcher said.
As genomic databases become more diverse and the ABCD kids get older, time will tell.
” Following these youth into early adulthood will help better inform how genetic risk is associated with things like screen time, psychopathology, symptoms, and sleep over the course of adolescence into early adulthood”, Paul said.
That will provide a more accurate picture of how these connections between your overall genetic risk and your behavior and traits change or do n’t change over time.
Overall, the present work demonstrates how the PheWAS technique can be employed to identify potential targets for upcoming prevention and early intervention strategies. In this study, several potentially modifiable targets, such as screen time and caffeinated beverages, were identified that could serve as early” catches” for reducing the risk of developing mental health concerns.
With limited well-developed GWAS available for other populations in the world, previous genome-wide studies of psychiatric diagnoses and phenotypes make use of data from people who are most genetically similar to European reference populations.
Therefore, the PheWAS’s main drawback was that only ABCD data from people with European ancestry could be used because the GWAS’s GWAS used data from European reference populations.
Although Paul argued that” that really limits the generalizability of these findings,” we should be able to expand the study population to include more people with genetically similar to other reference populations as more GWAS is discovered and more sophisticated polygenic score techniques are developed.
Funding: Data for this study were provided by the Adolescent Brain Cognitive Development ( ABCD ) study, which was funded by awards U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147 from the NIH and additional federal partners ( https ://abcdstudy .org/federal-partners .html ).
This study was supported by R01 DA054750. Authors received funding support from NIH: SEP was supported by F31AA029934. NRK was supported by K23MH12179201. AJG was supported by NSF DGE-213989.
ECJ was supported by K01DA051759. ASH was supported by K01AA030083. DMB ( R01-MH113883, R01-MH066031, U01-MH109589, U01-A005020803, R01-MH090786 ), RB ( R01-DA054750, R01-AG045231, R01-AG061162, R21-AA027827, R01-DA046224, U01-DA055367 ). NME was supported by NSF DGE-1745038.
About this information about genetics and mental health research
Author: Leah Shaffer
Source: WUSTL
Contact: Leah Shaffer – WUSTL
Image: The image is credited to Neuroscience News
Original Research: Closed access.
A phenome-wide association study of cross-disorder genetic liability in young people who are genetically similar to those in European reference populations was published by Nicole Karcher and colleagues. Nature Mental Health
Abstract
A cross-disorder genetic liability study of a phenome-wide association was conducted on young people who were genetically similar to those in European reference populations.
Use of hypothesis-free methods to identify connections between genetic risk for broad psychopathology and phenotypes measured in adolescence, including both markers of child psychopathology and intermediate phenotypes such as neural structure, which may provide insights into the development of epilepsy, may lead to the development of hypothesis-free methods.
Here we conducted an exploratory phenome-wide association study ( phenotype , n = 1, 271–1, 697 ) of polygenic risk scores ( PRS ) for broad-spectrum psychopathology ( that is, compulsive, psychotic, neurodevelopmental and internalizing ) in youth most genetically similar to individuals from European reference populations ( n = 5, 556, ages 9–13 ) who completed the baseline and/or 2-year follow-up of the ongoing Adolescent Brain Cognitive Development Study.
We found that neurodevelopmental and internalizing PRS were significantly associated with phenotypes across multiple domains ( neurodevelopmental, 190 and 214 ( 147 and 165 after pruning correlated phenotypes at an , r2 , of 0.6), internalizing, 124 and 183 ( 93 and 131 after pruning ) phenotypes at baseline and 2-year follow-up, respectively ), whereas compulsive and psychotic PRS showed zero and two significant associations, respectively, after Bonferroni correction.
Compulsive, psychotic and neurodevelopmental PRS were further associated with brain structure metrics, with minimal evidence that brain structure indirectly linked PRS to 2-year follow-up outcomes.
In middle childhood and early adolescence, genetic variation broadly manifests as behaviors, psychopathology symptoms, and related risk factors.
