Beyond the Genetics of Addiction

Most substances have well-known negative health consequences. Tobacco use is
the world*s leading cause of preventable death and is estimated to cause lung
cancer (70-90%), chronic respiratory disease (56-80%) and cardiovascular
disease (22%). The proportion of disease burden attributable to alcohol equals
around 4% of the global disease burden and this proportion was greatest in the
US and Europe. In contrast, some studies have reported beneficial effects of
(small amounts) of alcohol. Cannabis use is associated with increased risk for
the subsequent use of more harmful drugs such as cocaine and heroin (15) and
higher risk to psychotic symptoms (16). The effects of caffeine on human
behavior are diverse, but for the healthy adult population, moderate daily
caffeine intake is not associated with adverse health effects (17).

Substance use is common. Currently around 27% of Dutch population of 16 years
and older smoked, about 80% of the Dutch population (>= 12 years) reported to
drink alcohol and about 33% of 15-25 year olds have ever used cannabis (in
Dutch sample), (Central Bureau of Statistics, 2009). Caffeine is consumed
regularly by 80 to 90% of the adults as an ingredient of coffee, tea and other
products (18). The prevalence of substance use is higher in man than in women.
The pattern of substance use in the Netherlands is comparable with other
European countries and the US and Australia.

Twin studies have shown that both heritable and environmental factors play a
role in substance use and abuse. For initiation, the contribution of genetic
factors is somewhat lower than for dependence variables. Linkage and candidate
gene studies have revealed interesting candidate genes and chromosomal regions.
Recently, genome-wide association analyses have revealed several important
genes for substance related phenotypes.

The current project focuses on the sources of individual differences in the
liability to substance use, the comorbidity of different substances and the
consequences for health.

The proposal is organized around five interrelated themes:
1. Unravel the interplay between genetic and environmental influences on
substance use by using extended twin-family designs.
2. Disentangle genes and pathways involved in substance use with DNA-variant
data.
3. Explore differential gene expression patterns associated with substance use.
4. Test the added value of biomarkers for substance use (measured in blood or
urine) in understanding the individual variation in substance use.
5. Unravel relation between substance use and health by linking twin-family
data to medical databases.

Longitudinal twin-family study
A combination of genetic epidemiological, molecular genetic and
gene-environment interaction approaches will be used. Data will be analyzed
with multivariate methods, longitudinal models as well as other state-of-the
art methods.

All individuals registered with the NTR aged 18 years and older will receive an
invitation letter and an information brochure outlining the present study.
Participants will receive a link to the online survey and a (personal) login
code. If they do not complete the online version, they will receive a reminder
and a paper version of the list several weeks later. Participants are free to
complete the qeustionnaire within their own time in their own home and there
are no consequences to non-participation. Participants do receive (short)
personal feedback on their data. Final results (on group levels) of the survey
are published in scientific papers, on the NTR website and reported in the
yearly Twinfo magazine, that is send out to all individuals registered with the
NTR.

Participants are also invited to send us a sample of their scalp hair in order
to measure exposure to substances.