Introductory guide to the statistics of molecular genetics.
BACKGROUND
This introductory guide presents the main two analytical approaches used by molecular geneticists: linkage and association.


METHODS
Traditional linkage and association methods are described, along with more recent advances in methodologies such as those using a variance components approach.


RESULTS
New methods are being developed all the time but the core principles of linkage and association remain the same. The basis of linkage is the transmission of a marker along with a disease within families, whereas association is based on the comparison of marker frequencies in case and control groups.


CONCLUSIONS
It is becoming increasingly clear that effect sizes of individual markers on diseases and traits are likely to be very small. As such, much greater power is needed, and correspondingly greater sample sizes. Although non-replication is still a problem, molecular genetic studies in some areas such as attention deficit/hyperactivity disorder (ADHD) are starting to show greater convergence. Epidemiologists and other researchers with large well-characterized samples will be well placed to use these methods. Inter-disciplinary studies can then ask far more interesting questions such as those relating to developmental, multivariate and gene-environment interaction hypotheses.
Eley
Thalia C
TC
Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK. t.eley@iop.kcl.ac.uk
Rijsdijk
Frühling
F
D004812:Epidemiologic Methods; D008040:Genetic Linkage; D005821:Genetic Techniques / Q000706:statistics & numerical data*; D006801:Humans; D008967:Molecular Biology / Q000706:statistics & numerical data*