Genetics – Mind the Gap Blog

Genetics of dopamine and serotonin explain overlap in psychiatric disorders

Posted on January 20, 2022 by jcabanadominguez

Psychiatric disorders such as attention deficit / hyperactivity disorder (ADHD), autism, major depression or bipolar disorder, often overlap and occur together. For example, individuals with ADHD on average experience twice as many depressive symptoms as the general population without ADHD [1,2]. In addition to the distress and impairment that is brought on by a single psychiatric condition, having multiple conditions can hugely increase the severity of symptoms and hinder treatment. To better understand why these disorders overlap, we investigated the genetic risk factors that are shared among psychiatric disorders, and found several genes that play important roles in regulating two signaling-mechanisms of the brain: dopamine and serotonin [3].

Dopamine and serotonin are two important neurotransmitters (messengers molecules that transmit messages between brain cells) that control a wide range of essential functions in your brain (e.g. controlling your movements, cognition, motivation, regulation of emotions, and responding to reinforcement and reward). For that reason, alterations in these two systems have been related with the physiopathology of several psychiatric disorders, and also have been pointed as possible therapeutic targets for them.

We systematically explored the contribution of common variants in genes involved in dopaminergic and serotonergic neurotransmission in eight psychiatric disorders (ADHD, anorexia nervosa, autism spectrum disorder , bipolar disorder, depression, obsessive-compulsive disorder, schizophrenia and Tourette’s syndrome) studied individually and in combination. To do so, we used data from the Psychiatric Genomics Consortium (PGC, https://www.med.unc.edu/pgc/) to explore the entire genome in thousands of patients with different psychiatric conditions, which were compared with controls (individuals without any psychiatric condition).

In this way, we could identify variations in genes (and in groups of related genes) that confer susceptibility to a given disorder. For example, a gene named CACNA1C that is involved in the connectivity between brain cells, was found to contribute to both bipolar disorder and schizophrenia. Using this approach, we found 67 dopaminergic and/or serotonergic genes associated with at least one of the eight studied disorders, and twelve of them were associated with two conditions. Interestingly, five out of these twelve genes, including CACNA1C, belong to both the dopaminergic and serotonergic neurotransmitter systems, highlighting the importance of those genes that participate in both systems and their high interconnectivity. Next, we analyzed groups of genes that work together, and found that the dopaminergic genes have an important role in ADHD, autism, depression, and in the combination of all of the eight disorders that we studied. We also found that the group of serotonergic genes are relevant for the overlap between depression and bipolar disorder.

These results support the existence of a set of dopaminergic and serotonergic genes that increase the risk of having multiple psychiatric conditions. Having identified these genes, the next step is to investigate if any of these could be targeted by new drugs that directly influence specific parts of the dopaminergic or serotonergic system, compared to the more unspecific drugs that currently exist. That would be an important step for treating psychiatric comorbidity.

If you want to know more about this research, you can read our publication here.

This blog was written by dr. Judit Cabana-Domínguez. She is a postdoctoral researcher of psychiatric genomics at the Vall d’Hebron Research Institute (VHIR). The work described here is part of the CoCA project on comorbid conditions of ADHD.

References

McIntosch et al. (2009). Adult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD (nih.gov) Neuropsychiatric Disease and Treatment, 5: 137-150. doi: 10.2147/ndt.s4720
Di Trani et al. (2014). Comorbid Depressive Disorders in ADHD: The Role of ADHD Severity, Subtypes and Familial Psychiatric Disorders (nih.gov) Psychiatry Investigation, 11(2): 137-142. doi: 10.4306/pi.2014.11.2.137
Cabana-Domínguez et al. (2022). Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders. Translational Psyciatry, 12(1): 11. doi: 10.1038/s41398-021-01771-3

What have we learned about ADHD comorbidities?

Posted on July 2, 2021July 2, 2021 by Jeanette Mostert

After 5.5 years, the CoCA project has come to an end. In this large-scale European research project, an interdisciplinary group of researchers investigated comorbid conditions of ADHD. They particularly focussed on depression, anxiety, substance use disorder and obesity, as these conditions frequently co-occur with ADHD in adulthood.

What has this extensive study brought us? Experts dr. Catharina Hartman (University Medical Center Groningen, The Netherlands) and prof. dr. Andreas Reif (University Hospital Frankfurt, Germany) were invited by Jonathan Marx for an interview on the online radio program Go To Health Media. In this program they talk about several aspects of the CoCA project: How often do comorbid conditions co-occur with ADHD? What do the genetics of ADHD comorbidities tell us? What should clinicians do to prevent or reduce these comorbidities in ADHD?

As professor Andreas Reif summarizes at the end of the interview, the main things that we learned from the CoCA project are:

Comorbidity in ADHD is a very big problem. Adults with ADHD frequently have co-occuring conditions such as depression, anxiety, obesity and to a bit lesser extent substance use disorder.
The type and prevalence of comorbidities differ between men and women.
There is considerable genetic overlap between ADHD and comorbid conditions. We think that at least part of the overlap between comorbidities is caused by genetic effects (next to environmental effects that also play a role).
The dopamine system plays an important role in comorbidity, through influencing brain processes.
Disturbances in the circadian system (i.e. sleep cycle) are unlikely to play a causal role in these comorbidities, but they might be a consequence.
Clinicans should look out for comorbidities when they treat ADHD patients, and inform their patients about their increased risk to develop comorbidities so that they can take preventive measures (i.e. be careful with alcohol to avoid substance use disorder). Secondly, clinicians should actively look out for ADHD symptoms when treating conditions such as depression, anxiety, substance use disorder or obesity.

Watch the full interview with both experts by clicking on the image below:

More information about the CoCA project: www.coca-project.eu

IS GENETICS BEHIND THE CO-OCCURRENCE OF ADHD AND OTHER DISORDERS?

Posted on May 10, 2021May 12, 2021 by Bru Cormand

A group of researchers from Spain, The Netherlands, Germany, Estonia, Denmark and USA have joined efforts to gain insight into the genetics of ADHD and its comorbidities. This ambitious objective was addressed by the Work Package 2 of a big project called CoCA: “Comorbid Conditions of Attention deficit/hyperactivity disorder (ADHD)”, funded by the European Union for the period 2016-2021.

In psychiatry, the co-occurrence of different conditions in the same individual (or comorbidity) is the rule rather than the exception. This is particularly true for ADHD, where conditions like major depressive disorder or substance use disorders frequently add to the primary diagnosis and lead to a worse trajectory across the lifespan.

There are different reasons that may explain the advent of the comorbidities: Sometimes the two conditions have independent origins but coincide in a single patient. Comorbidity can also appear as a consequence of a feature of a primary disorder that leads to a secondary disorder. For example, impulsivity, a trait that is common in ADHD, can be an entry point to substance use. Comorbidity can also be the result of shared genetic causes. The latter has been the focus of our investigations and it involves certain risk genes that act on different pathologies, a phenomenon called pleiotropy.

Our project started with an approach based on the exploration of candidate genes, particularly those involved in neurotransmission (i.e. the connectivity between neurons) and also in the regulation of the circadian rhythm. We used genetic data of more than 160,000 patients with any of eight psychiatric disorders, including ADHD, and identified a set of neurotransmission genes that are involved at the same time in ADHD and in autism spectrum disorder [1]. In another study we identified the same gene set as involved in obesity measures [2].

Then we opened our analyses to genome-wide approaches, i.e. to the interrogation of every single gene in the genome. To do that we used different statistical methods, including the estimation of the overall shared genetics between pairs of disorders (genetic correlation, r_g), the prediction of a condition based on the genetic risk factors for another condition (polygenic risk score analysis, PRS) and the establishment of the causal relationships between disorders (mendelian randomization). As a result, we encountered genetic connections between ADHD and several psychiatric disorders, like cannabis or cocaine use disorders [3, 4, 5], alcohol or smoking-related phenotypes [6, 7, 8], bipolar disorder [9], depression [6], disruptive behavior disorder [10], but also with personality or cognition traits, like neuroticism, risk taking, emotional lability, aggressive behavior or educational attainment [6 , 11, 12, 13], or with somatic conditions, such as obesity [11, 12].

All these results and others, reported in more than 40 (!) scientific publications, support our initial hypothesis that certain genetic factors cut across psychiatric disorders and explain, at least in part, the comorbidity that we observe between ADHD and many other conditions. This information can be very useful to anticipate possible clinical trajectories in ADHD patients, and hence prevent potential negative outcomes.

Dr. Bru Cormand is full professor of genetics and head of the department of Genetics, Microbiology & Statistics at the University of Barcelona. He leads workpackage 2 of the CoCA project (www.coca-project.eu) on the genetics of ADHD comorbidity.

References

Genetic risk scores give new insights into the overlap between ADHD and insomnia

Posted on November 18, 2020November 19, 2020 by Victória

Psychiatric disorders, such as ADHD, are defined by categorical diagnostic borders: you either have it or you don’t. Research has shown that these borders do not accurately reflect what is happening on a biological level. In fact, these are complex traits that can be defined as quantitative characteristics that are present in people in different degrees. When you have or experience these traits in a very high degree, you may classify as having a psychiatric disorder. We also know that both genetic and environmental factors contribute to how much an individual is liable to ‘develop’ a psychiatric disorder, and that for each person, it is a different combination of such factors. This large variability between individuals is called heterogeneity.

The fact that ADHD is very often accompanied by other disorders (called comorbidities) also contributes to the notion that these conditions cannot be defined as a simple “yes/no” categorization. This refers to the notion of pleiotropy, meaning that one gene or biological mechanism can result in different outcomes. During my master’s thesis project, we investigated the genetic relationships between ADHD and insomnia, which is one of the most common conditions to co-occur with ADHD. We also looked into the role of depression, another common comorbidity, in the overlap between insomnia and ADHD.

Nowadays, there are very large datasets that we can use to explore such questions. In order to try to disentangle the genetic relationship between ADHD and insomnia, we calculated a genetic risk score for each individual. This method determines the estimated risk that an individual has to develop a certain trait based on their genetic make-up. We found that the genetic risk score for insomnia was linked to ADHD symptoms, and vice-versa: the genetic risk score for ADHD was linked to insomnia. We also observed a possible distinct genetic relationship between hyperactivity and inattention symptoms and insomnia: while we found that there was a shared genetic risk for insomnia and hyperactivity symptoms, we did not find this link with inattention symptoms.

Next, we tested the effect of depression in these relationships by the inclusion of depression-related variables as covariates in our analyses. We found that the association between genetic risk score for insomnia and ADHD symptoms was no longer considered significant, while the association between the genetic score for ADHD with insomnia was weaker. At last, we analysed the association of cumulative genetic risk for ADHD with insomnia while separating the individuals in two different groups by broad depression. The results suggest that genetic risk for ADHD is similarly associated with insomnia in individuals with and without depression. This indicates that the genetic relationship observed between ADHD and insomnia is not solely a consequence of the comorbidity between depression and the other two conditions.

The take-home message is that with these results we show that there are shared genetic influences between conditions that are traditionally defined as distinct or separate, so all three conditions might be all entangled in their underlying genetic factors. By advancing our understanding of how ADHD and its comorbidities are related, we can better refine the definition of ADHD. Also, from this research we learn more about the underlying mechanisms of ADHD (and associated conditions) from a biological (genetic) perspective. As the next step, we plan to include genetic data for separate ADHD symptom dimensions (hyperactivity and inattention), as well as depression in our analyses.

Victória Trindade Pons

I have recently concluded my Master’s in Biomedical Sciences at the Radboud University. This work was part of my final internship and was developed under the supervision of Dr. Nina Roth Mota in the Department of Human Genetics of the Radboudumc. This study is part of the CoCa project (Comorbid Conditions of ADHD), which has the aim to gain insight into the mechanisms underlying ADHD comorbidity and calculate the burden associated with such comorbidity for healthcare, economy, and society.

Picture from pixabay.

How psychiatric genetics can help to guide diagnostic practice and therapy

Posted on June 4, 2020 by Jeanette Mostert

Recently, professor Stephen Faraone from SUNY Upstate University in the USA gave a webinar about genetic research in psychiatry (especially ADHD) and how this can help to better understand diagnosis and provide better treatment. In this blog I will share with you some highlights from this webinar.

ADHD is a continuous trait in the population

ADHD is not something that you either have or don’t have. Rather, symptoms or characteristics of ADHD are present in the entire population, in varying severity. The system for psychiatric diagnoses is however based on categorical definitions that determine when a certain combination of symptoms and severity can be classified as a particular disorder. Although these categories can be of great help to provide public health data or determine insurance coverage, they often don’t really match individual cases. Hence there arise problems with heterogeneity, subtypes, subthreshold cases and comorbidity.

Genetic research has shown that psychiatric conditions such as ADHD are not caused by a few single genes, but rather by thousands or tens of thousands genetic variants that each contribute slightly to the ADHD risk. These so-called polygenic risk scores form a normal distribution across the entire population, with the majority of people having low polygenic risk scores (so a low to average risk of ADHD), while a small portion of individuals have a very low or very high risk. This adds to our understanding that ADHD is a continuous trait in the population.

*Image from the webinar by prof. Stephen Faraone*. *The higher the number on the x-axis, the higher the genetic risk of having ADHD. Negative numbers mean reduced genetic risk of ADHD.*

2. Comorbidity in psychiatry is the norm, rather than the exception

In the webinar, Stephen Faraone explains that in 90’s it was thought impossible that an individual can have both ADHD and depression. Now, we know better than that. There are substantial genetic correlations between different psychiatric disorders, meaning that the genes that increase the risk of for instance ADHD, also increase the risk of schizophrenia, depression, bipolar disorder, autism and tic disorder. This is further evidence that psychiatric conditions are not separate, categorial entities but rather arise from similar biological mechanisms.

3. Personalised medicine and pharmacogenetics are not yet sufficiently established to adopt widely and replace current medication on a broad scale

The second part of the webinar was about pharmacogenetic testing. This means that an individual’s genetic profile is used to determine whether a drug will be effective, and in what dose. Although this sounds promising, there is still a lot of discussion about the validity of such tests. This is due to varying results, differing protocols and large heterogeneity between studies. In some cases, pharmacogenetic testing can help to find the right treatment for an individual, for instance when this person is not responding well to regular treatment, but it is definitely not a fool-proof method yet. Better randomized controlled clinical trials are needed to improve reliability of these tests.

You can watch the full webinar here: https://www.youtube.com/watch?v=DLgqdJWZKIo

The genetics of having multiple mental health conditions

Posted on May 26, 2020May 26, 2020 by Jeanette Mostert

We know that psychiatric conditions have a strong genetic component. This means that genes play an important role in determining an individual’s risk or vulnerability to develop a psychiatric condition. However, there is evidence that there are genetic variants that increase the risk for multiple psychiatric disorders. This is called pleiotropy. Researchers of the “Cross-Disorder Group of the Psychiatric Genomics Consortium” have searched the entire genome of 727,000 individuals (of whom 233,000 were diagnosed with a psychiatric disorder) to identify genetic variants with such pleiotropy.

The researchers found one particular gene – called DCC – that increases vulnerability for all eight disorders that were investigated: ADHD, autism spectrum disorder, anorexia nervosa, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia and Tourette syndrome.

They also found more than 100 genetic variants that predispose to at least two psychiatric disorders, and around 20 variants that are associated with four or more. This means that the genes that contain these variants can be interesting to further understand why certain individuals are more vulnerable to develop psychiatric illnesses than others.

One of the researchers, professor Bru Cormand, explains more about this research in this blog.

Further reading: Cross-Disorder Group of the Psychiatric Genomics Consortium (2019): Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell, 179(7): 1469-1482.e11.

Professor Cormand is involved in the CoCA research consortium where he investigates the genetic overlap between ADHD, major depression, anxiety disorder, substance use disorder and obesity. To read more about this, see for instance this other blog by him and dr. Judit Cabana Dominguez.

The genetic architecture of the brain

Posted on April 17, 2020 by Jeanette Mostert

Genes play a big role in determining the architecture of our brain: the way it’s folded, the thickness of the outer layer, and the way different brain areas are connected. By combining data from all over the world, a large collaboration of researchers from the ENIGMA consortium has now identified almost 200 genetic variants that are involved in this brain architecture. These findings can help us to further understand the genetics of brain disorders.

Our genes contain the blueprint of our bodies. They contain information about how our cells function, and they determine for instance the colour of our eyes and hair, or whether we like cilantro (coriander) and bitter tastes. For some traits we know very well how they are influenced by genes. Eye color for instance is coded by only a few genes. But for many other traits such as height and personality, many different genes are involved. In addition, other (non-genetic) factors also influence these traits, such as malnutrition that can cause stunted growth.

The architecture of the brain is influenced by a large numer of genes, of which we still know very little. To investigate this, researchers combined genetic data of over 50.000 individuals with MRI-data. MRI-scans can show in detail the thickness of the outer layer of the brain, where all the brain cells are (also called the grey matter). They can also be used to measure how much this layer is folded, which gives information about the total surface of this outerlayer. This brain architecture is unique to every individual. The extent of the folds and the thickness of the outer layer have previously (in other research studies) been linked to cognitive abilities and various neurological and psychiatric disorders, such as Alzheimer’s disease, schizophrenia, depression, autism, and ADHD. It is therefore helpful to understand the genetics of this architecture, because it will help us to better understand the genetic mechanisms of these conditions.

The findings from this research study are also explained in this video:

This important research can only be done by combining a lot of data and collaborating with a large number of scientists and institutes. The ENIGMA consortium has been set upt to facilitate this kind of world-wide collaboration. The research that has now been published is the combined effort of more than 360 scientists from 296 departments across 184 different institutions and universities. They also made their results downloadable so that everyone who is interested can have a closer look.

The full publication can be found here: https://science.sciencemag.org/content/367/6484/eaay6690

See also our previous blogposts about these topics:

Large genetic studies on ADHD: https://mind-the-gap.live/2019/07/17/no-i-do-not-have-adhd-i-am-just-busy-but-still-very-interesting-for-genetic-studies/
The cortex and ADHD (another example of research from the ENIGMA consortium): https://mind-the-gap.live/2019/05/03/the-cortex-and-adhd-the-second-project-of-the-enigma-adhd-collaboration/
Connectivity between brain regions and ADHD: https://mind-the-gap.live/2016/12/29/connectivity-adhd-brain/
What it’s like to participate in an MRI experiment: https://mind-the-gap.live/2020/02/08/on-a-coalmine-and-an-mri-scanner-is-it-fun-participating-in-delta/

From genes to driving schools: an Estonian program to reduce traffic accidents

Posted on February 3, 2020February 3, 2020 by Jeanette Mostert

Driving is dangerous. 1.35 million people die from road accidents every year, according to the World Health Organization [1]. Young people who just obtained their driving license, and especially young men, are at the highest risk for accidents. They are often seeking sensation, are more likely to take risks, and are more prone to take impulsive or thoughtless decisions while driving. To target this specific group, Estonian researchers have developed a training program for driving schools to make people aware of their impulsive tendencies.

Genetic predictors of traffic accidents

Interestingly, this Estonian research group that is led by professor Jaanus Harro specializes in genetics. Next to studying rats, Harro wanted to also investigate impulsive and aggressive behavior in humans. To measure this objectively outside of a laboratory setting they used data on traffic offences and accidents. Harro and his group found that a particular variation in the gene called 5-HTTLPR was associated with the number of speeding offences and traffic accidents [2]. People who have the short version of this variant are less likely to be caught for speeding or be involved in accidents, compared to those with the long variant.

The gene 5-HTTLPR is an important player in the serotonin system in the brain. Serotonin is a messenger molecule with many functions, one of them being the regulation of mood, impulsivity and aggression. Some people are more prone to act without thinking, or without considering the consequences, and this can partly be explained by genetics.

Reducing impulsive driving behavior

So should only people with the short version of 5-HTTLPR be allowed to drive? No, Harro and his team came up with something better: a program to reduce impulsive behavior on the road. They gave this to students who were learning to drive. In the training, students discussed their own impulsive tendencies, and ways to overcome these tendencies. There was also a control group that did not receive this extra lesson. Four years after obtaining their licenses, the group that received the training had been less involved in traffic violations and accidents than the control group. What’s more, those individuals with the long variant of 5-HTTLPR – so the ones who are more likely to be impulsive, based on this gene – benefited from the training the most.

For the driving schools the main implication of this experiment is that it is very beneficial to incorporate awareness training about impulsivity into driving lessons. Already eight driving schools in Estonia are providing the program to their students. The genetic findings however are mainly of interest to the researchers, who are hoping to gain a better understanding of impulsive and aggressive behavior. In addition to the serotonin-gene, they have found that genetic variations in the noradrenaline and dopamine system are also linked to traffic offenses and speeding, and to the effectiveness of the training [3, 4]. And just recently, they found that the neuropeptide orexin is linked to both aggression and to the prevalence of drunk driving and traffic accidents [5].

Beyond genetics

In addition to genes, other factors such as age, intelligence, and stressful life events influence the risk of offences and accidents as well, but we still know very little about how this works. That is why Harro and his team are now investigating the interactions between genes and environment. This research is part of the horizon2020 projects CoCA and Eat2beNICE. Ultimately, through a better understanding of our biology they hope to improve the way that people behave on the road, thereby reducing the number of accidents.

Meanwhile, Jaanus Harro travels to ministries and other governmental organizations in Estonia and Finland, to convince them to implement the training program on a national level, and to provide funds for further research. And in case you wonder about Harro’s own driving habits: although he acknowledges that he is quite impulsive, he assures us that he has learned to keep this under control while driving.

Jaanus Harro was recently interviewed by Science Business about this topic. Parts of this blogpost ar based on this interview. You can read the article here: https://sciencebusiness.net/keeping-drivers-impulses-check

References

[1] https://www.who.int/news-room/fact-sheets/detail/road-traffic-injuries (accessed 3 January 2020).

[2] Eensoo, Paaver, Vaht, Loit & Harro (2018). Risky driving and the persistent effect of a randomized intervention focusing on impulsivity: The role of the serotonin transporter promoter polymorphism. Accident Analysis and Prevention, 113, 19-24. https://www.ncbi.nlm.nih.gov/pubmed/29407665

[3] Paaver, Eenso, Kaasik, Vaht, Mäestu & Harro (2013). Preventing risky driving: A novel and efficient brief intervention focusing on acknowledgement of personal risk factors. Accident Analysis and Prevention, 50, 430-437. https://www.ncbi.nlm.nih.gov/pubmed/22694918

[4] Luht, Tokko, Eensoo, Vaht & Harro (2019). Efficacy of intervention at traffic schools reducing impulsive action, and association with candidate gene variants. Acta Neuropsychiatrica, 31, 159 – 166. https://www.ncbi.nlm.nih.gov/pubmed/31182183

[5] Harro, Laas, Eensoo, Kurrikoff, Sakala, Vaht, Parik, Maëstu & Veidebaum (2019). Orexin/hypocretin receptor gene (HCRTR1) variation is associated with aggressive behaviour. Neuropharmacology, 156. https://www.ncbi.nlm.nih.gov/pubmed/30742846

“No I do not have ADHD, I am just busy!”, but still very interesting for genetic studies!

Posted on July 17, 2019 by Janita Bralten

Do you sometimes find it difficult to pay attention? Can you be very disorganized at times, or very rigid and inflexible? Although difficulties with attention, organization and rigidity are symptoms of psychiatric disorders, these traits are not unique to people with a diagnosis. And that is very useful for studying the genetics of psychiatric disorders.

Being easily distracted, liking things to go in a certain way, having a certain order in the way you do things, these might all be things you recognize yourself (or someone you know) in, while you (or they) are not diagnosed with any psychiatric disorder. We actually know that many of these symptoms are indeed found in a range in the general population, with some people showing them a lot, some a little and some not at all. If these symptoms are also present in people without a diagnosis then why should we only study people with a diagnosis to learn more about the biology of symptom-based disorders?

Many psychiatric disorders, like attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are disorders that ‘run in the family’. Using family-based and genetic studies it was found that they are actually highly heritable. However the underlying genetic risk factors turned out to be difficult to find. Enormous samples sizes (comparing more than 20 000 people with the disorder to even more individuals without the disorder) were needed to robustly find just a few genetic risk factors, although we know that many more genetic factors contribute. Even though these disorders are highly prevalent, collecting genetic data on psychiatric patients for research is still challenging. Using population-based samples – that include all varieties of people from the general population – can be a good alternative to reach large sample sizes for powerful genetic studies.

Taking together the fact that psychiatric-like symptoms are also, to a certain degree, present in the general population, and the fact that genetic studies can benefit from large(r) sample sizes to find genetic associations, it can be very interesting to study psychiatric-like traits in population-based samples. This is indeed what happened in the field of psychiatric genetics. The first proof-of-concept studies were able to show an astonishing overlap in genetic factors of more than 90% between ADHD and ADHD symptoms in the general population. Our own research group was able to show that certain autistic traits, like rigidity, indeed share a genetic overlap with ASD and that genes that were previously linked to ASD show an association to autistic traits in the population. These results show that genetic factors involved in disorder-like traits are overlapping with genetic factors involved in the clinical diagnosis, and therefore can indeed be used to study the biology of psychiatric disorders.

So next time you feel distracted/rigid/disorganized, don’t get discouraged, but consider signing up for a genetic study. Science might need you!

Janita Bralten is a postdoctoral researcher at the department of Human Genetics in the Radboud university medical center, Nijmegen, the Netherlands. Her research focusses on the genetics of psychiatric disorders.

Cocaine dependence is in part genetic, and it shares genetic risk factors with other psychiatric conditions and personality traits.

Posted on July 4, 2019 by jcabanadominguez

Cocaine is one of the most used illicit drugs worldwide and its abuse produces serious health problems. In Europe, around 5.2% of adults (from 15 to 64 years old) have tried cocaine, but only 20% will develop addiction. Why? Genetics is part of the answer. Cocaine dependence is a complex psychiatric disorder that results from the interaction of both environmental and genetic risk factors. Twin and adoption studies indicate that genetic alterations contribute substantially to cocaine dependence susceptibility, which has an estimated genetic load (heritability) as high as 65-79%. Although many studies with focus on candidate genes have been performed, only a few risk variants for cocaine dependence have been identified and replicated so far.

https://www.
flickr.com/photos/30478819@N08/24042216187

In this study we performed a meta-analysis of genome-wide association studies (GWAS) of cocaine dependence using more than 6,000 European ancestry individuals. This approach allowed us to inspect a huge number of genetic variants distributed all along the genome that are common in the general population. We identified a gene (HIST1H2BD) associated with cocaine dependence that is located in a region on chromosome 6 enriched in genes that encode histones, proteins that combine with DNA, protecting it and contributing to the activation (or inhibition) of genes. Some of these genes have previously been associated with schizophrenia.

Several studies have shown that substance use disorders (SUD), and especially cocaine dependence, co-occur in patients with other psychiatric disorders and personality traits. Such comorbidity is associated with increased severity for all disorders, although it is unclear whether this relationship is causal or the result of shared genetic and/or environmental risk factors. We calculated the shared genetics (genetic correlation) between cocaine dependence and six comorbid conditions. For the first time we found significant genetic correlation with attention deficit/hyperactivity disorder (ADHD), schizophrenia, major depression and risk- taking behavior. We also used another approach (polygenic risk score analysis, PRS) to prove that all tested comorbid conditions are associated with cocaine dependence status, suggesting that cocaine dependence is more likely in individuals that carry genetic risk factors for the tested conditions than in those that do not.

To our knowledge, this is the largest reported GWAS meta-analysis in European-ancestry individuals with cocaine dependence. We identified suggestive risk factors for the disorder in several genomic regions and found evidence for shared genetic risk factors between cocaine dependence and several co-occurring psychiatric traits. However, the size of the sample is still limited and further studies are needed to confirm our results.