Welcome!

Introduction

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Marek Brandys Krakow (Krakau), Poland Utrecht, Netherlands Rudolf Magnus Institute of Neuroscience and Rintveld Eating Disorder Unit

Marek Brandys Utrecht Medical Center

Krakow

What do I do in Utrecht?

Management of the database Communication between University center and ED clinic Statistical and theoretical interpretaion of results Conceptual work – links between genetic variance and phenotypic variance and animal models of AN

Database

Database includes blood samples (DNA) and phenotypic data (diagnoses and questionnaires) At the moment there are about 200 samples of AN patients that we have blood from – Still growing – 750 controls Some of them were additionally phenotyped with several questionnaires – OCD symptoms (Y-Bocs) – State anxiety (STAI) – Questionnaires on acivity, non-questionnaire measures of activity – TCI (Cloninger’s) – EDI-2 – BAT (Body Attitude Questionnaire) – Apart from that a “standard” type of data is collected (weight, height etc.) – Perhaps some neuropsychological tests in the future

What’s the procedure?

Research design

Correlations between canditate gene variants and phenotypic variants Genome-wide association study (GWAS) Activity Based Anorexia (ABA) model – animal model of Anorexia

Genetic variation

99,9 % of the genome shared Genetic variance in the remaining 0,1% SNP’s (single nucleotide polymorphisms) CTCCACAGCACTCC [C/T] GACAGCCCCG CTCCACAGCACTCC [C/T] GACAGCCCCG CC CT TT

Endophenotypes

Poliethiology of AN Difficulty of investigating poliethiological pathologies In order to tackle this problem we can use an endophenotype construct (deconstruction of a phenotype) Endophenotype and genes

Which endophenotypes?

To be decided… – OCD symptoms (Y-Bocs) – Trait anxiety (STAI) – Questionnaires on acivity – TCI (Cloninger’s) – BAT (Body Attitude Questionnaire) – Apart from that a “standard” type of data is collected (weight, height etc.) – Perhaps some neuropsychological tests in the future

Candidate genes

DRD2 and DRD4 (Dopamine receptors) UCP2/UCP3 (Uncoupling proteins – involved in thermoregulation) PTP1P (may be associated with OCD symptoms) CCK (Hormone released after a fatty meal)

How is genotype associated with a disease?

A liability-threshold model – there are susceptibility alleles – a genetic liability (vulnerability) is continuously distributed among population – there is a threshold of liability – a disease can develop when susceptibility alleles exceed the threshold of liability – Gene-gene interactions (epistasis) – a gene variant will only exert its effect in the presence of another gene variant – Gene-environment interactions – a gene variant will only exert its effect under certain environmental conditions

Gene

What’s the hassle for?

Function (product) Drug Genotype Therapy Improvement of the understanding of etiology Improvement of the diagnostic criteria

Plans for the near future

Continuation of education within the field of genetics and molecular biology Getting familiar with statistical procedures / packages required for these kinds of studies Working on hypotheses, in the context of phenotypic data that we have Improvement of the database Translation of results from animal studies (ABA) to human research ...

Acknowledgements

Prof. Roger Adan Dr Annemarie van Elburg Dr Unna Danner Dr Martien Kas Sietske  Judith Hendriks and other people from RMI Interns at the ED Unit Rintveld