Escolar Documentos
Profissional Documentos
Cultura Documentos
Consultant (Mayo)
Janssen, Mitsubishi Tanabe Pharma Corporation, Myriad,
Sunovion, Teva Pharmaceuticals
Lower
respiratoryinfections
2. Diarrheal
diseases
3. Perinatal
conditions
4. Unipolar major
depression
5. Ischemicheart
disease
6. Cerebrovascular
disease
7.
Tuberculosis
8.
Measles
9. Roadtraffic
accidents
10. Congenitalanomalies
20. Alcohol use
22. Bipolar disorder
*DALY = disability-adjusted life year composite measure of time lost due to premature mortality & time lived with disability. Murray and Lopez, 1996.
Developed Regions
1. Lower respiratory
infections
1.
2.
2.
3.
Cerebrovascular disease
4.
5.
Alcohol use
6.
Osteoarthritis
Diarrheal diseases
3. Perinatal
conditions
4.
Unipolar major
depression
5. Ischemic heart
disease
6. Cerebrovascular
disease
7.
Tuberculosis
8.
Measles
9. Road traffic
accidents
9.
Self-inflicted injuries
ALY = disability-adjusted life year composite measure of time lost due to premature mortality & time lived with disability. Murray and Lopez, 1996.
World
1. Lower respiratory
infections
1.
2.
Diarrheal diseases
2.
3.
Perinatal conditions
3.
Cerebrovascular disease
4.
4.
5.
5.
Alcohol use
6.
Osteoarthritis
6. Cerebrovascular
disease
7.
Tuberculosis
8.
Measles
9.
Self-inflicted injuries
Developed Regions:
15-44 years old
1. Unipolar major
depression
2.
Alcohol use
3. Road traffic
accidents
4.
Schizophrenia
5. Self-inflicted
injuries
6.
Bipolar disorder
7.
Drug use
8. Obsessivecompulsive disorders
9.
Osteoarthritis
10. Violence
DALY = disability-adjusted life year composite measure of time lost due to premature mortality & time lived with disability. Murray and Lopez, 1996.
1 % US population
Bipolar II (m / D)
Sex
Onset (average)
1-2% US population
Equal distribution
First impairment (age 15-19)
First treatment (age 20-24)
First hospitalization (age 25)
Recurrence
Average 2.7 - 9 years
Suicide
~35% attempt, ~9% succeed
Predominant phase of illness - depression
Frye et al., 2009; Novick 2010; Bostwick 2003
Years
Kraepelin, 1921
Established in 2009
Co-PIs: Mark Frye and Joanna Biernacka
DNA matched to a rigorous clinical phenotype to facilitate
genomic and other biomarker studies of:
disease risk
treatment response
Consents
This
week
Total
Mayo
16
832
30
802
Austin
96
LCOH
11
370
U of MN
Clinica
Alemana
Enteredthis
week
Total
Mayo
784
89
Austin
89
18
352
LCOH
348
76
17
59
U of MN
58
Clinica
Alemana
UANL
UANL
Total
27
1374
72
1302
Total
16
1279
Screenfails,
withdrawn
Total
CAB Recommendations
Diagnosis and treatment selection, particularly in youth /
young adult life, were key recommendations
Recommendations to consider
an electronic consenting process
educational DVD about the study to potentially engage a
younger audience and to evaluate if this mode of
information delivery was associated with a greater level of
understanding of informed consent
As of March 2014
38,000 people have enrolled, provided blood
samples and completed self-report and physician
questionnaires
heritability
Percentage
BMI
(McElroy et al.,
2011 MFMER | slide-26
Interaction between
TCF7L2 and BMI (p2df = 2.85*10-8)
TCF7L2
Prior associations:
Type2diabetes: TCF7L2-BMI interaction
Glucose metabolism
(Obesity, Cancer)
2011 MFMER | slide-29
MAF2
ORMA2
Reference
A/G
0.18
1.18
rs9804190
C/T
0.236
0.21
0.86
rs1099433
C/T
0.063
0.06
1.35
rs1938526
A/G
0.075
0.06
1.32
CACNA1C rs1084863
C/T
0.385
0.40
1.08
G/A
0.385
0.34
1.11
rs10245823 G/A
0.397
0.37
1.11
rs4765913
0.276
0.21
1.15
Gene
SNP
Major/minor
allele
ODZ4
rs1257677
5
ANK3
2
rs1006737
T/A
rsreferencesequencenumber(NationalCenterforBiotechnologyandInformation)
Result
Relevance
SLC6A4
L/S
5HT2C
C/C
CACNA1C
G/A
MTHFR
C/T
Reduced conversion to
methyl folate
CYP2D6
*2/*4
Intermediate metabolizer
CYP2C19
*1/*17
Ultrarapid metabolizer
Slides courtesy of Dr. Paul Croarkin
2011 MFMER | slide-34
Result
Relevance
DRD2
NS/NS
No clinical significance
ANK3
C/C
No clinical significance
(ankyrin proteins-role in
sodium channel function)
COMT
Val/Met
No clinical signficance
Val variant catabolizes
dopamine 4x greater rate
CYP3A4/5
*3/*3
Poor metabolizer
Pharmacogenomics
Research implications
Pathophysiology of complex genetic, multifactorial
illnesses
Development of new medications that are more
efficacious, better tolerated, more personalized
Clinical uses
Prediction of dose, adverse effects, therapeutic
response
http://www.coligen.org/images/clg-logo-gruen.gif
NationalInstituteofMentalHealth(NIMH)
InternationalGroupforTheStudyofLithium
TreatedPatients(IGSLI)
2011 MFMER | slide-39
Masoliver3766
Ferreira4369
Mayo113182
Summary
OR
Meta-analysis marginally significant evidence of association between S allele and AIM+ (p=0.059)
Freq.
Score
Simp
Maxstat
simp
Global
simp
L-A-10
0.344
-2.448
0.012
0.047
0.020
L-G-12
0.027
-1.555
0.14
--
S-A-10
0.214
0.144
0.86
--
L-A-12
0.136
0.965
0.31
--
S-A-12
0.225
1.034
0.28
--
PharmacogenomicTargetsinBipolarDisorder
MayoClinic
SupportedbytheMarriottFoundation
UniversityofMinnesota
Scott J. Crow, M.D.
AdvisorBoard
RobertM.Post,M.D.
George Washington University
PediatricKeyOpinionLeaders
GabrielleA.Carlson,M.D.
Stony Brook
MelissaDelBello,M.D.
University of Cincinnati
KikiChang,M.D.
Stanford School of Medicine
CathrynGalanter,M.D.
SUNY Downstate
StevenHirschM.D.
Bethesda
VictoriaCosgrovePhD.
Stanford School of Medicine
PeterJensen,MD
REACH Institute
FlavioKapczinskiM.D.
UT Houston
KathrynR.Cullen,M.D.
University of Minnesota
KarenDineen-Wagner,M.D.,
PhD.
The University of Texas Medical
Branch
Steering Committee Co-Chair
AnneDuffy,M.D.;FRCPC
University of Calgary
GianricoFarrugiaM.D
Mayo Clinic
PaulE.KeckJr.M.D.
Lindner Center of Hope
MartinSchallingM.D.
Karolinska Institutet
PamelaSklarM.D.,Ph.D.
Mount Sinai Hospital
AnaAndreazza,PhD
University of Toronto
BonnieKlimesDougan,PhD.
University of Minnesota
EricYoungstrom,M.D.
University of North Carolina at
Chapel Hill
MayoClinicDepressionCenter
Mark A. Frye M.D. Director
MarkA.FryeM.D.MarinVeldic,M.D.WilliamBobo,M.D.KatherineMooreM.D.
SimonKungM.D.BrianPalmerM.D.PaulCroarkin,D.O.JarrodLefflerPh.D.
OsamaAbulseoudM.D.Doo-SupChoiPh.D.JoannaBiernackaPh.D.SusannahTyePh.D.
MayoClinicDepressionCenter