KAROLINSKA INSTITUTET International Biobank and Cohort Studies: Developing a Harmonious Approach...

KAROLINSKAINSTITUTET

International Biobank and Cohort Studies: Developing a Harmonious Approach

February 7-8, 2005, Atlanta; GA

Karolinska Institutet

GenomEUtwin Karolinska

Institutet Biobank LifeGene

Jan-Eric LittonKarolinska Institutet, StockholmSweden


Karolinska InstitutetStockholm, Sweden


Stockholm… an archipelago with 30.000 ilands


A letter from King Karl XIII to the Collegium Medicum in 1810 authorized the immediate establishment of a ”college for the corps of field surgeons”.

War and cholera War and cholera led to the royal decree ...led to the royal decree ...


From a school for army From a school for army surgeons to a surgeons to a medical universitymedical university

1810 The Royal Carolinska Medico-Surgical Institute was founded ”for the creation of skilled Army Surgeons”.

1811 Jöns Jacob Berzelius became one of KI’s first professors and laid the foundation for the Institute’s natural-scientific orientation.

1895 Alfred Nobel appointed Karolinska Institutet to decide who should be awarded the Nobel Prize in Physiology or Medicine.

1993 A comprehensive reorganization of KI began: 150 departments became 27.


GenomEUtwin

• The European Consortium of Twin Registries for Analyses of Complex Traits; www.genomeutwin.org

• Aims to capitalize special advantages of Europe in population genetics

•The goal is to identify critical genetic and life-style risk factors for common diseases using European strengths in genetics, epidemiology and biocomputing

QuickTime och enTIFF (LZW)-dekomprimerare

krävs för att kunna se bilden.


GenomEUtwin

• Funded by EU as one of three Centers of Excellence in Genomics in 2002, PI: Leena Peltonen

• Twin cohort from Denmark, Finland, Italy Netherlands, Norway and Sweden (England and Australia) over 600 000 twin pairs total, 65% dizygotic

•MORGAM cohort from 9 European countries, total of > 144 000 participants




GenomEUtwin

• Twin Cohorts have been used for decades to estimate to role of genetics in the background of common diseases

• Gathering phenotype info for decades

• In SwedenCivic # 1947Swedish Cancer Registry 1958The Cause of Dead Registry, started 1756, modern classification 1961




TwinNET

• Ten first monthsa database structure established

• Database completionA common, secure database established in Europe for all relevant scientific information in GenomEUtwin


TwinNET

•EUid number (EUIDNUM) 752000021210

–The EUidnumber consists of four parts:

Country code 3 digits – ISO 3166

Randomized number 7 digits

Identification number 1 digit

Check sum 1 digit


TwinNET

VARIABLE FORMAT STANDARD – DRAFT 1 Subject identifier Country and/or center Pair number/family number Twin number Individual specific – permanent Date of birth Gender Date of death Place of birth (region of birth) Zygosity Birth weight Changeable phenotypes/socio-demographic issues Weight Height (include age of assessment, Time of assessment, and Mode of assessment for each item)


Appendix A – Migraine Phenotype

Version: 1.1

Author:Ann Björklund

Participants:Ingunn BrandtLars HvidbergAnne Leinonen

Phenotype Group of Migraine:Elles MulderDavid Gaist

Mikko KallelaDorret Boomsma

Aarno Palotie


TwinNET

2 Data format

Variable Name Description Type Length ValuesMIGR_DIAGNOSIS Type of

migraineNUMBER 2 1 – Migraine with aura.

2 – Migraine without aura3 – Not classified.4 – Migraine with or withoutaura.5 – Never had migraine97 - Irrelevant/non- -

participant/non-response98 - Do not know99 - Unknown

MIGR_LEVEL Differentlevels ofdiagnosticaccuracy.Level Abeing thelowest andlevel Dbeing thehighest.

NUMBER 2 1 – Level A. Affirmativeresponse to at least one of thequestions (see section 1)2 – Level B. Self-reportedmigraine.3 – Level C. Interview-basedmigraine.4 – Level D Diagnosedmigraine.97 - Irrelevant/non-

participant/non-response98 - Do not know99 - Unknown

MIGR_DATE_DIAG Date ofdiagnosisi

DATE 8 YYYYMMDD - Year, month,dayYYYYMM15 - day unknownYYYY0701 - day andmonth unknownNULL/blank - Irrelevant/non-participant/non-response,Irrelevant/structural,Do not know, Unknown

MIGR_DATE_ERROR

Error codefor date ofmigrainediagnosis

NUMBER 1 1 - Date is complete2 - Day is missing, coded 153 - Day and month aremissing, coded 07016 - Irrelevant/non-participant/non-response7 - Irrelevant, structural8 - Do not know9 - Unknown

Description of the migraine phenotypeMigraine is a complex neurovascular disorder and can be divided in migraine with aura andmigraine without aura. These subtypes are clincally distinguishable but it is as yet unclearwhether different genes are involved. The levels as described below reflect different levels ofdiagnostic accuracy with level A being the lowest, Level D being the highest.

Level B is the minimal condition for initiating a genome scan for migraine. Those countrieswho are currently at level A will therefore need to confirm their diagnosis by using theextensive migraine screening questionnaires (Palotie, Kallela, and Ferrari, 2003) that havebeen validated in a Finnish population sample. The questionnaire will also require translation-back-translation checking, as well as review by national migraine specialists for appropriatewording.

Level A: Affirmative response to at least one of the following questions: Have you ever had migraine? Have you ever had visual disturbances of 5 to 60 minutes’duration followed by

headaches? Has a doctor ever told you that you have migraine? Have you suffered from headache attacks during the previous year and -if so- were

attacks associated specifically with any of the following symptoms: visualdisturbances, nausea or vomiting, unilateral location.

Level B: Self-reported migrainePositive classification for migraine with or migraine without aura based on the extensivescreening questionnaires (under construction). Classification is unconfirmed by a structuredinterview conducted by trained personnel, neurologist or physician.

Level C: Interview-based migrainePositive classification for migraine with aura or migraine without aura by a (locally designed)questionnaire that includes the IHS criteria. Classification has been confirmed by telephone orhome interviews conducted by trained personnel.

Level D: Diagnosed migrainePositive classification for migraine with aura or migraine without aura based on IHS criteriaduring a face-to-face interview and examination conducted by a neurologist or physician.


Federated data approch

• Data stay untouched–Integrates heterogeneous local or remote data sources through wrappers

• Just need to know what data should be available to whom and how to access them• It makes all data look like it is one virtual database hiding the data layer complexity

ODBC – JDBC and moreODBC – JDBC and more


TwinNET

Relational wrappers list

DB2 family

Informix (Informix Client SDK)

Oracle (SQLNet or Net8 client)

MSQL Server (ODBC driver version 3.0 or later)

Sybase (Sybase open client)

Teradata (Teradata CLI)

ODBC (ODBC driver version 3.x)

Non-relational wrappers list

Lotus Extended search

Excel

Flatfile (CSV format)

XML (1.0 specifications)

OLE DB

BLAST

Documentum (Documentum client API)

Entrez (version 1.0)


TwinNET

Genotypes

FinnishTwin

Registry

SwedishTwin

Registry

FinnishTwin

Registry

Genotypes

SwedishTwin

Registry

Federated database HUB

GenomEUtwin centres databases GenomEUtwin user


TwinNET December 2004

GT GT GT

FGCHelsinki

Mol Med Rudbeck labUppsala

Genotypes

SMdb

Database federation – Information Integrator

Phenotypes

Genotypesubmission database

Helsinki

SSH SSH Excel sheet SSH

WE

B

IBM xSeries 3252xOpteron, 4GB, SAN

DK

SQ

L

Stockholm

NO FI SE


Karolinska Institutet Biobank

• Karolinska Institute Biobank constitutes a national, non-commercial resource for collection, handling and storage of human biological material aiming at promoting scientific excellence within molecular andgenetic research.

• Biobank Informatic is a central part of the Karolinska Institutets Biobank


Biobank Information Management System - vision

A system that will enable a researcher to search and navigate the enormous amounts of information available for samples and their donors in various data sources.


Biobank Information Management System

BIMSLIMS

Freezer

WebInterface

LabRobot

DB:s

OtherBiobanks



WebSphere Application Server

WebSphere Portal

DB2Portal

Database

Web S

erv

er Portal

Admin

LDAP Directory

Web Interface

Data Collection

DDQB QueryInterface

DDQBData

Abstraction

Replication

Architectural Overview Diagram

DB2II Data Federation

LIMSDB

BRAINDB

I nternet

VPN

PIMSDB

SwedishTwin

Register

FederatedDB

BIMSResearch

Data

BIMSAdminData

Data Analysis

Std DataAnalysis

Tools

UserAdmin

StudyMgmt

WebSphere Application Server

WebSphere Portal

DB2Portal

Database

Web S

erv

er Portal

Admin

LDAP Directory

Web Interface

Web Interface

Data Collection

DDQB QueryInterface

DDQBData

Abstraction

Replication

Architectural Overview Diagram

DB2II Data Federation

LIMSDB

LIMSDB

BRAINDB

I nternet

VPN

BRAINDB

BRAINDB

I nternet

VPN

I nternet

VPN

PIMSDB

PIMSDB

SwedishTwin

Register

SwedishTwin

Register

FederatedDB

BIMSResearch

Data

BIMSAdminData

Data Analysis

Std DataAnalysis

Tools

UserAdmin

StudyMgmt



DDQB- Absract Data Model

DatabaseF

F FF

FF

F

C

C

C User View

Access Methods

Abstract Query

Abstract Query

Data Abstraction Model (DAM)


LifeGene

A Swedish Population-based

Project on

Lifestyle, Genomics and Health


LifeGene

Study of aetiology of diseases with high health care and economic impactProspective highly motivated and well characterized cohort with 5-800,000 Ascertainment of nuclear familiesAges 0-39: infections, asthma and allergy, obesity and diabetes, mental disorders and cognitive dysfunctionAges 40-64: CVD, diabetes, neurodegenerative disorders, cancer


[email protected]

KAROLINSKA INSTITUTET International Biobank and Cohort Studies: Developing a Harmonious Approach...

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