Team 1: Negative Psychological Attributes Mirjam Sprangers, Ph.D. Academic Medical Center/University of Amsterdam Frank Baas, Ph.D. Academic Medical Center/University of Amsterdam Nick Martin, Ph.D. University of Queensland Miriam Mosing, M.Sc. University of Queensland Genetic Disposition & Patient Genetic Disposition & Patient - - reported Quality of Life Outcomes reported Quality of Life Outcomes Rochester, MN, February 26 Rochester, MN, February 26 – – 28, 2009 28, 2009
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Team 1: Negative Psychological Attributes
Mirjam Sprangers, Ph.D.Academic Medical Center/University of Amsterdam
Frank Baas, Ph.D. Academic Medical Center/University of Amsterdam
Nick Martin, Ph.D.University of Queensland
Miriam Mosing, M.Sc.University of Queensland
Genetic Disposition & PatientGenetic Disposition & Patient--reported Quality of Life Outcomesreported Quality of Life Outcomes
Rochester, MN, February 26 Rochester, MN, February 26 –– 28, 200928, 2009
Acknowledgements
Prof. dr. Dick SwaabNetherlands Institute for Neuroscience, AMC, University of Amsterdam
Dr. Eric RuhéDepartment of Psychiatry, AMC, University of Amsterdam
Judith van der Harg, Linda Hoogland, Tessa van
der Maaden, Boy Vissers, Nathalie Audureau,
Willemieke Kouwenhoven, Eva NaninckMaster students Neurobiology, University of Amsterdam
Negative Psychological Attributes:
Definition
• Psychological functioning: psychological distress <-> positive sense of
well-being
• Focus of effort: Negative side of this continuum;
"normal" feelings of distress
Negative Psychological Attributes:Biological and genetic research
• Mostly conducted in pathology and psychiatry
• We expect a similar biological substrate for non-
pathological negative affect
• The focus is on major depressive and anxiety disorders
• There is a large variety of depressive and anxiety disorders
• The following summary can therefore only be
sketchy and incomplete
Question 1
Which potential biological pathways have been considered and/or shown to describe a possible genetic disposition for negative
psychological affect?
Question 2
Which genes and genetic variants have been considered and/or shown to have a potential association with negative psychological affect?
The problem of gene finding in relatively The problem of gene finding in relatively frequent diseasesfrequent diseases
•• Is a single mutation responsibleIs a single mutation responsible
•• Usually notUsually not
•• Is a single gene responsibleIs a single gene responsible
•• Probably notProbably not
•• How do we solve this problemHow do we solve this problem
COMPULSIVE SCALE in schizophreniaCOMPULSIVE SCALE in schizophrenia
30
20
10
0
COMT genotype
Y-B
OC
S t
ota
l s
co
res
N=12 N=34 N=12
Val/ValN=23
Val/MetN=51
Met/MetN=12
P=0.005
P=0.042 P=0.022
Question 3
What datasets are available to explore the association of genes and negative psychological affect?
Available Australian DataAvailable Australian Data
•• The Australian Twin Registry (ATR) The Australian Twin Registry (ATR) -- a a volunteer register.volunteer register.
•• Data have been collected on a range of Data have been collected on a range of phenotypes (e.g. Alcohol/Drug phenotypes (e.g. Alcohol/Drug consumption, personality etc.) since 1978 consumption, personality etc.) since 1978 (>50,000 individuals)(>50,000 individuals)
•• GWAS data available for almost 10,000 GWAS data available for almost 10,000 adults and 4,000 adolescentsadults and 4,000 adolescents
•• Of the phenotype data how many variables Of the phenotype data how many variables are related to Quality of Life (are related to Quality of Life (QoLQoL) and also ) and also have genotype information available?have genotype information available?
•• Which studies explore phenotypes Which studies explore phenotypes related to related to QoLQoL? ?
•• How many individuals have How many individuals have information available on these information available on these phenotypes of interest?phenotypes of interest?
•• Genotyped?Genotyped?
•• Un/related?Un/related?
OLDER COHORT
(born 1892-1963)YOUNGER COHORT
(born 1964-1971)
Australian Twin Registry
Recruitment Pools
Studies
Mailed Questionnaire
Telephone Interview
In-person Testing or
Measures Taken
relatives ofAlcohol Cohort 1
twins recruited
older twins recruited since
1981
Figure 1. Flowchart of studies that have collected data related to quality of life.
families from Finnish Twin Cohort:selection based on
All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped
individualsindividuals and genotypedand genotyped individualsindividuals and genotypedand genotyped individualsindividuals and genotypedand genotyped
All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped All All phenotypedphenotyped
individualsindividuals and genotypedand genotyped individualsindividuals and genotypedand genotyped individualsindividuals and genotypedand genotyped
…….. if phenotypes shared.. if phenotypes shared 29202920 988988
FemalesFemales 77857785 24822482
MalesMales 51745174 13001300
How many days during the last year How many days during the last year has illness kept you away from your has illness kept you away from your
normal work?normal work?
Canberra Study, SSAGA1, Canberra Study, SSAGA1,
Alcohol Cohort 1 and 2, Alcohol Cohort 1 and 2,
Relatives of Alcohol Relatives of Alcohol
Cohort 1 and 2Cohort 1 and 2
(17(17--96 years)96 years)
NN females/malesfemales/males
Total # Total # phenotypedphenotyped individualsindividuals 1799017990 10284/769710284/7697
Total # genotyped individualsTotal # genotyped individuals 90749074 6266/27846266/2784
Total # unrelated individualsTotal # unrelated individuals 28452845 NANA
How would you rate your health at How would you rate your health at present?present?
How would you rate your How would you rate your emotional wellbeing at present?emotional wellbeing at present?
Data can be contributed Data can be contributed
Can be increased (Can be increased (phenotypingphenotyping vs. vs. genotyping)genotyping)
Other Existing Datasets:
General Population
• Framingham Sleep Heart Health Study - N = 2772; - Negative affect: SF-36 items (4 items of mental health scale)- GWAs- Open access via dbGAP web portal - Request on behalf of the Consortium submitted
• Framingham Share- N = 3000 (Offspring of above study) - Negative affect: SF-36 items (4 items of mental health scale)- GWAs
Other Existing Datasets:
Disease Populations
• GAIN Major Depressive Disorder StudyNetherlands Twin Register (NTR) and Netherlands Study ofDepression and Anxiety (NESDA) biobanks- Co-Principal Investigator: Dorret Boomsma- N = 1821 MDD cases and N = 1822 controls- range of questionnaires- GWAs available- Open access via dbGAP web portal
Future Datasets
• General population
- LIFEGENE: Swedish general population, N = 500,000
Co-Principal Investigator: Nancy Pedersen
Negative affect: CES-D
Collection of blood
• Disease populations- Breast and prostate cancer: N = 10,000s Swedish patients
Co-Principal investigator: Per Hall- Congenital heart disease: N = 1,400 Dutch patients
Co-Principal investigator: Mirjam Sprangers
Question 4
How would you design a new prospective study to explore the association of genes and negative psychological affect?
New Prospective StudyOperationalization of negative psychological affect
A) Anxiety/depression subdomains or individual items of generic quality-of-life questionnaires, e.g.:
New Prospective StudyOperationalization of negative psychological affect
A)Anxiety/depression subdomains or individual items of generic quality-of-life questionnaires, e.g.:
• SF-36 Health Survey (SF-36; SF-12)
• Euroqol EQ-5D (EQ-5D)
• Nottingham Health Profile (NHP)
• Psychological General Wellbeing Index (PGWI)
• Affect Balance Scale (ABS)
New Prospective StudyOperationalization of negative psychological affect
B) Anxiety and depression questionnaires, e.g.:
New Prospective StudyOperationalization of negative psychological affect
B) Anxiety and depression questionnaires, e.g.:
• Hospital Anxiety Depression Scale (HADS)
• Center for Epidemiologic Studies-Depression scale (CES-D)
• State Trait Anxiety Inventory (STAI)
• Inventory of Depressive Symptomatology (IDS-SR)
• Beck Depression Inventory (BDI)
• General Health Questionnaire (GHQ)
New Prospective StudyGenes and Genotyping
Common disease – common variant
All patients share some genetic variants in a set of
genes. The combination determines disease
susceptibility. Variants have small effects.
Common disease-rare variant
All patients are unique have different (private)
mutations. Effect size can be large or small.
Types of Types of geneticgenetic variationvariation