The Older 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 ten 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 study

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 subsequent questionnaire. 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.

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 below.

Table 1. The Components of the Finnish Twin Cohort

Follow-up in 2010

A fourth questionnaire will be sent to the older twin cohort in 2010 to assess self-reported health, functional capacity and lifestyle factors, thus enabling a 35 year study with four time points of measurements, and multiple outcomes. In 2007, there were more than 10,000 twins in the cohort alive and resident in Finland born between 1945 and 1957. Among them are about one third MZ and two thirds DZ pairs with both twins alive and resident in Finland. The follow-up will permit powerful analyses of the change and stability of smoking patterns and related traits from early adulthood onwards. The baseline age was 18-27 years (in 1975), and their age in 2010 will be 53-62 years of age.

In addition to repeating the same smoking history items given in 1975, 1981 and 1990, we aim to include all the background, health and health-related items asked in all previous surveys, and relevant ones asked in only one or two of the surveys. Of these twins, 2182 have already given a DNA sample in earlier studies of disease-related phenotypes. They will be requested to give a new consent for genotyping of study-related traits, while others will be requested to give a saliva sample for DNA.

Data from the younger Finntwin12 and Finntwin16 studies with four measurement points in each will be examined for the study of initiation and early stages of smoking.