The Older Finnish Twin Cohort

The older Finnish Twin Cohort study started in 1975, with follow-up questionnaires in 1981 and 1990. There has been registry-based follow-up, and numerous clinical and intensive studies on smaller numbers of twin pairs as described earlier (Kaprio & Koskenvuo, 2002). For the past 5 years, our focus has been on registry-based follow-up, reporting on studies in which data collection has been completed, and participation in multicentre studies.

The Family Study of Nicotine Dependence is part of an international consortium led by Dr Pam Madden, and primarily funded from 2001 to 2005 by NIH to address the genetics of nicotine dependence. The study sample consists of families ascertained for heavy smoking in at least two siblings, who have been sampled from amongst the older twin cohort (born before 1958) first assessed by questionnaire in 1975. Data on lifetime tobacco use, nicotine dependence, and associated factors were obtained by a detailed diagnostic telephone interview (average duration 120 minutes) and subsequentquestionnaire. The interview yields diagnoses of nicotine dependence defined using Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) and the Fagerström Test for Nicotine Dependence, and the questionnaire yields a quantitative measure of nicotine dependence from the Nicotine Dependence Syndrome Scale (Shiffman et al., 2004). In addition, multiple other measures of smoking history including details on initiation, cessation and withdrawal symptoms are assessed as well as alcohol use, psychiatric comorbidity and demographics. DNA samples are collected by blood sampling at local health centers. A total of 2265 individuals from 762 families participated; 59% of invited families participated. Participants were somewhat older than nonparticipants, more often women than men, but participants and nonparticipants did not differ in amount smoked based on earlier questionnaire information.

GenomEUtwin (PI Leena Peltonen) is a European Union-funded project running from 2002 to 2007 that combines twin cohorts/registers from seven European countries (Denmark, Finland, Italy, the Netherlands, Norway, Sweden and United Kingdom) and Australia. The GenomEUtwin sample consists of almost 700 000 twin pairs. We have participated in studies of height, BMI, migraine, cardiovascular risk factors, coronary heart disease and stroke, and longevity as part of the project. In the project, standard operating procedures and standardized data reporting procedures have been developed. To permit multicentre analyses without jeopardizing data security, a federated database
has been created. A 2003 special issue of Twin Research was devoted to the project, to which the reader is referred (Peltonen, 2003)

The Finnish Twin Study on Aging (FITSA) lead by Professor Taina Rantanen is a study of genetic and environmental effects on the disablement process in older female twins. Four hundred and fourteen female pairs aged 63 to 76 years old and alive in 2000 were initially contacted. Further description of the participation in FITSA was reported earlier (Pajala et al., 2004; Tiainen et al., 2004; Tiainen et al., 2005). The final study sample at baseline included 103 MZ and 114 DZ complete pairs, who participated in a 1-day laboratory assessment of functional abilities (such as muscle strength, walking speed, balance), and health status (such as hearing ability and risk of falls during a 1-year follow-up) at the University of Jyväskylä. Three years later an invitation to participate in the follow-up examinations was sent to all baseline participants. As 106 individuals consented to participate solely in an interview, the follow-up sample consisted of 145 MZ and 168 DZ individuals after excluding deceased subjects and refusals. These 313 twins participated in the laboratory measurements in addition to the interview.

In collaboration with the University of Turku and the Turku PET Centre, elderly (born before 1938) MZ and DZ twins are being screened to identify twin pairs discordant with respect to Alzheimer's disease. Screening will be completed in 2006. Out of a large number of twin pairs, we first identified a small sample of MZ pairs discordant for dementia. These pairs were then invited for clinical assessment and underwent extensive neuroimaging using MRI and PET imaging (Järvenpää et al., 2004; Järvenpää et al., 2003a; Järvenpää et al., 2003b). We have shown that binge-drinking in middle age predicts dementia 25 years later (Järvenpää et al., 2005)

Datasets

The Finnish Twin Cohorts (Kaprio et al., 1978; Kaprio, 1994) form a national resource for genetic epidemiological studies. Twins and their families have been ascertained in three stages from the Central Population Register for studies of the genetic and environmental determinants of common, chronic diseases. In this paper we will focus on recent and in-progress research based on the older twin cohort. A comprehensive list of publications and a review of studies completed by the early 1990s was published in 1994 (Kaprio, 1994).

Cohort of Older Like-sexed Twins (Born Before 1958)

The older part of the Finnish Twin Cohort consists of all Finnish twin pairs of the same gender born before 1958 with both co-twins alive in 1975. These twin pairs were selected from the Central Population Registry of Finland in 1974. Three surveys of the entire cohort have been carried out. The first questionnaire was mailed to all pairs in August-October 1975. Two follow-up questionnaire studies have been carried out in 1981 and 1990. Twin zygosity was determined by a validated questionnaire methods initially in the entire cohort (Sarna et al., 1978). In studies of selected twin pairs, genetic markers have been
used for validation. The total number of MZ and DZ twin pairs was 13,888 in the beginning of prospective follow-up in August 1975.

Expansion of Older Cohort in 1996 to Include Opposite-sex Pairs

In 1996, opposite-sex (OS) twins born 1938--1949 have been identified from the Central Population Registry. So far, questionnaire data and DNA samples from over 1500 pairs have been collected in 1997. These are pairs in which one or both of the twins reported that they have been diagnosed with one of selected chronic diseases. This new material represents a substantial new population of sibpairs, while permitting the expansion of the twin design to assess sex by gene, sex by environment as well as sex by gene by environment interactions. Questionnaire data have been used to study sex-limitation models such as for height
(Silventoinen et al., 2001), but also as phenotypic information to identify affected sibpairs for molecular genetic studies as described in Table 1.

Table 1

The Components of the Finnish Twin Cohort