World Congress of Psychiatric Genetics

Christian and Olly recently participated in the World Congress of Psychiatric Genetics (WCPG) in Montreal.

Rücklab closely collaborates with Psychiatric Genomics Consortium (PGC) within genetics of depression, anxiety disorders, OCD, suicide and ICBT treatment response. This year, Christian and Olly presented two posters highlighting their ongoing work in prediction of ICBT treatment outcome where polygenic risk scores are used as one of potential predictors.

Olly presenting one of the posters to curious conference attendees.

Here are some take away-points from the conference by Olly:

  • Larger sample sizes: Sample sizes are becoming larger, increasing the number of identified genetic risk variants associated with liability to psychiatric disorders. Multiple biobanks and clinical research groups combine their data with direct-to-consumer genetic testing companies, such as 23andMe, to generate and metaanalyze large case/control samples (n > 1 million) 
  • The need for more globally inclusive samples: The focus is now on increasing cross-population samples as European ancestry has been so far disproportionately overrepresented in the studies, hindering progress and more importantly, putting most of the global population at a disadvantage in terms of new health-related discoveries and potentially further widening health disparities.
  • Discoveries through non-western samples: PGC has a working group dedicated to cross-population analyses that has shown some advances in increasing data sourcing from African, East Asian and Hispanic ancestries. In one talk, it was demonstrated that Africa alone has over 3000 distinct genetic groups and some drug discoveries would be impossible without their data.
  • Whole-genome studies become more accessible: It appears that as sequencing is becoming more affordable, whole-exome and whole-genome analyses will take over the most widely used genome-wide association studies which are cheap and accessible but limited to common genetic variants.
  • Societal and clinical implications of genetic testing: Finally, there were many important discussions on the future and ethics of direct-to-consumer genetic testing. Scientific community realises its role in elevating public awareness of what these data can and cannot tell and how they can be acted on. There are many  potentially dangerous misinterpretation of e.g. polygenic risk scores versus absolute/relative risk.

Genetics of OCD

Julia Boberg – psychologist, PhD student and research group member – recently published a review article on the genetic epidemiology and molecular genetics studies of obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms.

Results

OCD is a heritable, polygenic disorder with contributions from both common and rare variants, including de novo deleterious variations. Multiple studies have provided reliable support for a large additive genetic contribution to liability to OCD, with discrete OCD symptom dimensions having both shared and unique genetic risks. Genome-wide association studies have not produced significant results yet, likely because of small sample sizes, but larger meta-analyses are forthcoming. Both twin and genome-wide studies show that OCD shares genetic risk with its comorbid conditions (e.g. Tourette syndrome and anorexia nervosa).

Conclusions

Despite significant efforts to uncover the genetic basis of OCD, the mechanistic understanding of how genetic and environmental risk factors interact and converge at the molecular level to result in OCD’s heterogeneous phenotype is still mostly unknown. Future investigations should increase ancestral genetic diversity, explore age and/or sex differ- ences in genetic risk for OCD and expand the study of pharmacogenetics, gene expression, gene × environment interactions and epigenetic mechanisms for OCD.

Read the full article here.

Jim Crowley affiliated to our group

Assistant Professor James J. Crowley is now affilated to Karolinska Institutet and our group. Jim is currently at the Department of Genetics at the University of North Carolina at Chapel Hill. Check out some his recent publications here. We are very proud to have him at KI.

Evelyn Andersson sucessfully passed her half-time seminar

Evelyn Andersson a week ago passed her half time seminar with flying coulors. We wish to thank the board: Prof Jerker Hetta, Prof Bo Melin and Assoc Prof Patrik Magnusson. The PhD is on genetics and CBT.

Evelyn Andersson at her half-time seminar
Evelyn Andersson at her half-time seminar

Half-time seminar

PosterEvelyn Andersson will have her half-time seminar for her PhD (“From DNA to Therapy – Predictors, Candidate Genes and a Gene x Environment study with national register data”) on March 28 at 2 pm at Askö, M57, Karolinska Huddinge.

New study: genetic variants in the monoamine system and CBT outcome in social phobia

In a collaboration between Karolinska Institutet and Uppsala University, we studied three genetic polymorphisms in the monoamine system (5-HTTLPR, COMT val158met, TPH2 G-703T) and outcome of cognitive behavioral therapy (CBT) in social anxiety disorder (SAD) in over 300 patients. This is one of the largest genetic studies ever made on adults with SAD and CBT outcome. Monoamine-related gene polymorphisms have previously been tied to amygdala reactivity, treatment efficacy and fear extinction processes and was hereby reasoned to influence the outcome of CBT. However, none of our polymorphisms were associated with CBT outcome at long term follow-up. In our subsamples we found contradictory significant effects immediately after treatment. Even though CBT is an effective treatment of anxiety disorders, many patients (25-50%) do not respond sufficiently. Therefore, there is a need to improve not only the treatments but also how patients are selected for treatment in order to optimize the efficacy. Therapygenetics attempts to explore the relationship between genetic variation and psychological treatment response. Ultimately, such knowledge could be used to tailor therapies based on patients’ biological markers, which in turn, could improve therapeutic outcome.

Image
Lead author Evelyn Andersson.