Summary: A large international study of over 21,000 identical twins has identified genetic variants that influence how individuals respond to life experiences, affecting traits such as anxiety, depression, and autistic traits. By analyzing genetic differences in identical twins, researchers discovered that certain genes make people more or less sensitive to environmental exposures.

These findings suggest that the same experience may have drastically different effects depending on a person’s genetic makeup. The study offers insight into gene-environment interactions and how they influence neurodevelopment and psychiatric traits.

Key Facts:

• Twin-Based Design: Studied 10,896 pairs of genetically identical twins to isolate environmental effects.
• Trait Sensitivity: Genes linked to growth, immune function, and stress regulation influence psychiatric traits.
• Individual Response: Sensitivity genes explain why similar experiences impact people differently.

Source: King’s College London

An international team of researchers led by King’s College London have identified genetic factors that may make some individuals more or less sensitive to the environments they experience.

Published in Nature Human Behaviour, the study examined how individuals’ varying sensitivity to environmental factors can influence levels of ADHD symptoms, autistic traits, anxiety and depression symptoms, psychotic experiences and neuroticism.

The researchers at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, University College London, Queen Mary University of London and 23 universities around the world combined data from up to 21,792 identical twins (10,896 pairs) from 11 studies to discover genetic variants linked with environmental sensitivity. This is the largest genome wide association study (GWAS) of identical twins to date.

They identified several genetic factors that were linked with differences in environmental sensitivity within identical twin pairs. The interaction between these genetic factors and environmental exposures could explain differences in susceptibility to psychiatric and neurodevelopmental conditions.

Dr Elham Assary, Postdoctoral Researcher at King’s IoPPN and first author of the study, said: “Differences in individuals’ sensitivity to life experiences can explain why the same negative or positive experiences may have varying effects on people’s mental health, depending on their genetic make-up.

“Our findings suggest that specific genetic variants influence how environmental exposures impact psychiatric and neurodevelopmental symptoms.”

Both genes and life experiences shape a person’s characteristics, including the expression of conditions such as depression, anxiety, ADHD and autism. The interaction between genetics and environmental exposures are thought to contribute to diversity in a wide range of traits within all species.

But, identifying the genes that are involved in this pathway has proved challenging, especially for complex psychological traits.

Identical (monozygotic) twins are almost 100 per cent genetically identical, meaning that any differences in their characteristics are likely to be due to the environments they each experience.

If a monozygotic twin pair carries genes that make them more sensitive to the effects of the range of unique environments they each experience (for example, relationships or traumatic events), they will be more dissimilar to their co-twin, compared to another pair that is less sensitive to these experiences.

Using this information, it is possible to scan the genome to identify the genes that impact variations in environmental sensitivity.

Among the genetically identical twins, the researchers discovered genes that explained variations in autistic traits, anxiety, depression, psychotic-like experiences and neuroticism, reflecting heightened environmental sensitivity.

They found that genes linked with growth factors – biological molecules which play important roles in neurodevelopment, immune function and the central nervous system – were associated with variation in autistic traits.

Genes related to reactivity to stress were linked to variation in depression symptoms. Genes involved in regulating catecholamines – a group of hormones involved in response to stress – were linked to variation in psychotic-like experiences.

Professor Thalia Eley, Professor of Developmental Behavioural Genetics at King’s IoPPN and joint senior author of the study, said: “These findings confirm that genes influence psychiatric and neurodevelopmental traits partly through affecting how people respond to the world around them.

“Some people are more sensitive to their circumstances, and this can be positive in good circumstances but can make life more challenging than for others in stressful circumstances.”

Professor Neil Davies, Professor of Medical Statistics at UCL Division of Psychiatry and joint senior author of the study, said:  “This study demonstrates first, the importance of family-based designs and twin studies in providing compelling evidence about how our genomes interact with the environment to affect mental health.

“Second, it highlights that our scientific research is so much stronger when we collaborate internationally.”

Professor Patricia Munroe, Professor of Molecular Medicine at Queen Mary University of London and joint senior author of the study, said: “The results from this study provide an important step forward in disentangling gene-environment interactions for psychiatric traits and provide a framework for similar investigations in other traits.”

Funding: The study received funding from Wellcome and used twin datasets from around the world: the Danish Twin Registry, Finnish Twin Cohort, Murcia Twin Registry, Netherlands Twin Registry, Older Australian Twins Study, Swedish Twin Registry, Twins Early Development Study, TwinsUK and QIMR Berghofer twin studies.

About this genetics and mental health research news

Author: Amelia Remmington
Source: King’s College London
Contact: Amelia Remmington – King’s College London
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes” by Elham Assary et al. Nature Human Behavior

Abstract

Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect.

Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods.

We combined data from 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct one of the largest genome-wide association study meta-analyses of monozygotic phenotypic differences, in children, adolescents and adults separately, for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism and wellbeing.

The proportions of phenotypic variance explained by single-nucleotide polymorphisms in these phenotypes were estimated (h² = 0–18%), but were imprecise.

We identified 13 genome-wide significant associations (single-nucleotide polymorphisms, genes and gene sets), including genes related to stress reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences.

This is the largest genetic study of monozygotic twins to date by an order of magnitude, evidencing an alternative method to study the genetic architecture of environmental sensitivity.

The statistical power was limited for some analyses, calling for better-powered future studies.