twin registers: the danish twin registry axel skytthe, institute of pubic health, university of...
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Twin Registers:The Danish Twin Registry
Axel Skytthe, Institute of Pubic Health, University of Southern Denmark
Twin RegistersCollection of individuals from multiple births …
Register:Longitudinal dimension - maintenanceContinued follow-upBig numbers …
Purpose:Provide basis for studies to disentangle the importance of genetic, familial and environmental factors on life events, health conditions and diseases
Types of Twin RegistersLocal registers vs. national registers
Specific vs. general Focus on a specific phenotype Wide range of phenotypes
Population-based vs. Disease-based
AscertainmentIdentification methods
Self-reported Advertisments Hospital-based Medical birth records Population registers
Follow up / Tracing Population registers Death registers Relatives Probate court
Twin Registers - ExamplesNordic twin registers
SwedenEstablished in late 1950’s
Birth cohorts 1886-2008
Approx. 97,000 twin pairs
Norway3 separate twin cohorts compiled at different research institutions, and each
compiled with specific research agendas
Birth cohorts from 1895-1960 and 1967-
Approx. 67,000 twin pairs
Not consistently followed up
FinlandFirst cohort established 1975 from Central population register
Approx. 65,000 twin pairs
Twin Registers - ExamplesEuropean
Sct Thomas, UKEstablished 1990
Volunteers
Focused on diseases occuring in women -> predominantly same-sexed female twin pairs
The Netherlands Twin RegisterEstablished 1986
Predominantly young twins registered at birth
Includes other family members as well
Approx. 30,000 win pairs
East Flandern Prospective Twin SurveyInitiated in 1964
Registered at birth – collection of data related to twin maternities
Approx 7,000 twin pairs
Italian Twin RegisterInitiated 1996 as a register of ”possible twins” – 600,000 pairs
Enrolled approx. 4,500 twin pairs
Twin Registers - ExamplesOutside Europe
NAS-NRC Twin Registry of WWII Military Veteran TwinsEstablished in 1960’s
Only white male-male twin pairs – 16,000 twin pairs
Born 1917-1927
Both served in the armed forces
Minnesota Twin Registry (USA)Established in 1983
Birth record based …
Vietnam Era Twin Registry (USA)Established mid 1980’s
Only male-male twin pairs – 7,369 twin pairs
Both serving in the military during 1965-1975
Identification based on miltary records
Danish Twin Registry (DTR) – Old Cohorts
Local vicars searched births registers and reported twins
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1870 1890 1910 1930 1950 1970 1990 2010Year
Cohorts 1870 - 1930
The Danish Twin Registry
DTR – Old Cohorts
Local vicars searched birth registers and reported twins
Twins were traced through municipial population registers, death registers, probate courts, family members
Period: 1954 - 1979
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Cohorts 1870 - 1930
The Danish Twin Registry
The Old Core of DTR
The Old Core ...
Data processing...
DTR – Young Cohorts
Identified and traced through the national Civil Registration System
Selection criteria: Children of mothers giving birth to more than one child within 3 days
Period: 1991-1992
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Cohorts 1870 - 1930 Cohorts 1953 - 1982
The Danish Twin Registry
DTR – Young Cohorts
DTR – Middle Cohorts
Mainly identified and traced through the CRS, followed by questionnaire of twin status
Selection criteria: Persons born the same day and same place, and given the same surname at birth
Period: 1996-1998
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Cohorts 1870 - 1930Cohorts 1931 - 1952Cohorts 1953 - 1982
The Danish Twin Registry
DTR – Child Cohorts
Identified through the Medical Birth Registry as all multiple births
Traced through CRS
Period: 2001-2010
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Cohorts 1870 - 1930Cohorts 1931 - 1952Cohorts 1953 - 1982Cohorts 1983 - 2008
The Danish Twin Registry
DTR – Number of Twin Pairs - Gender
Gender Twin pairs born
Cohort M/M M/F F/F Unknown Total
1870-1910 3898 5142 4197 0 13237 37914
1911-1930 2948 1 3201 0 6150 22700
1931-1952 5928 6602 4312 239 17081 24574
1953-1967# 3779 3825 3276 15 10895 14332
1968-1982# 3702 2921 3362 227 10212 9856
1983-2000 5251 5555 4990 402 16198 16195
2001-2008 3429 4304 3297 83 11113 11113
Total§ 28935 28350 26635 966 84886 136684
# Twin pairs born outside Denmark are included in DTR (678 twin pairs)§ In addition 775 triplets and 22 quadruplets are included in DTR
Assesment of ZygosityQuestionnaire method
Similarity questions: 1. Do you and your twin look - like two ordinary siblings?
- like two peas in a pod?
- not very much alike? 2. In school, is/was it difficult for your teachers and friends to tell you apart? 3. Is/was it difficult for your family and friends to tell you apart? 4. In childhood, did you and your twin have both the same eye color and the same hair
color?
Biological material Serological markers Genetic markers
Zygosity Assesment - Accuracy
MZ accuracy DZ accuracy Total accuracy
Men (N= 342) 92% (155/169) 99% (172/173) 96% (327/342)
Women (N= 525) 96% (229/239) 96% (275/286) 96% (504/525)
Christiansen et al., Twin Res 2003;6:275-278
Zygosity Assesment - Accuracy
Birth cohorts MZ accuracy DZ accuracy Total accuracy
1900-1930 (N = 250) 94% (94/100) 93% (139/150) 93% (233/250)
1931-1952 (N = 143) 97% (72/74) 99% (68/69) 98% (140/143)
1953-1982 (N = 474) 93% (218/234) 100% (240/240) 97% (458/474)
All cohorts (N = 867) 94% (384/408) 97% (447/459) 96% (831/867)
Christiansen et al., Twin Res 2003;6:275-278
DTR – Number of Twin Pairs - Zygosity
Zygosity
Cohort MZ DZ-SS DZ-OS UZ Total
1870-1910 1834 3342 5142 2919 13237
1911-1930 1635 3326 1 1188 6150
1931-1952 2451 5406 6626 2598 17081
1953-1967# 2470 3871 3825 729 10895
1968-1982# 2788 2887 2921 1616 10212
1983-2000 1769 4182 5555 4692 16198
2001-2008 - - 4304 6809 11113
Total§ 12947 23014 28374 20551 84886
# Twin pairs born outside Denmark are included in DTR (678 twin pairs)§ In addition 775 triplets and 22 quadruplets are included in DTR
Basic DataCore data
Identification Gender Date of birth, place of birth Name & address Vital status (incl. date of death, emigration) Protection status Zygosity
DTR – Present Core Data Structure
Person•Id•PNR•Date of Birth•Gender•Name•Address•Vital status•Date of Vital st.•Access
Pair•Pair-Id•Tw1-Id•Tw2-Id•Type
Ascertainment•Method•Date of Ascert
Zygosity•Pair-Id•Zygosity•Method•Date of assessment
Parent-Child•P-Id•C-Id•Type (biol/legal)
Spouse•Sp-Id•Marital status•Date of M.St.
Additional DataTest results (performance tests, physical, cognitive)
Family (Spouse(s), Parents, Children)
Biological material Blood spots on filter paper Full blood samples Cheek swab Hair
Pictures
SurveysQuestionnaire surveys
Large scale self-administered questionnaire surveys (1966, 1994, 2002, 2003)
Interview-based surveys (LSADT 1995-2005, MADT 1998)Disease-specific surveys
Asthma Low back pain Epilepsy Arthritis
Clinical studies GEMINAKAR – 1 day test program (e.g. oral glucose test, fat tolerance test,
fitness, EKG, BP, blood samples, etc)
Middle-aged Twins 2008Biobank with samples from 13,000 twins
Collection period 2008-2011
Birth cohorts 1931-1969
Full blood samples
Short questionnaire Life style Health problems Medicine SES
Physical and cognitive performance
Height, weight
Data from National Registers
PopulationRegister
Deathcauses
CancerRegister
HospitalDischargeRegister
MedicalBirth
Register
DTR
Requirement:
Unique Personal Identification
Number (PIN) used in all registers
Linkage to Databases and Registers
Registration unit of database? Hospital discharge register:
Admissions
Diagnoses
Operational procedures
Organisation of database? Cross-sectional vs. longitudinal
Truncation? Which period is covered by database?
Studybase? Both twins should be at risk
Twins and Register-based Research
Advantages Data exist Big numbers No dropout No bias Population-based
Caution Zygosity needed Not all phenotypes available Administrative registers – not always suited for research