Software
for genetic association analyses in case-parent triads, case-control
data (or combined case-parent control-parent triads), with SNP
haplotypes
NOTE: THIS IS A
DEPRECATED VERSION. PLEASE USE THE LATEST VERSION OF HAPLIN,
available from http://www.uib.no/smis/gjessing/genetics/software/haplin
Web page last updated: April 29, 2009
Most recent version: Haplin 3.0, uploaded April 29, 2009
Background
HAPLIN is free software written for the purpose of analyzing
case-parent triad (trio) data and/or case-control data. Some of the
main features of Haplin are:
Analyses of the case-parent triad design, the case-control
design, and "hybrid" designs using combinations of case-parent triads
and control-parent triads.
Optimal use of designs with missing genotypic data, for
instance a single SNP has not been typed for some individuals, or when
the case father has not been genotyped at all, or when the control
parents are not available.
Estimation is based on haplotypes, for instance SNP haplotypes,
even
though phase is not known from the genetic data.
Estimation of relative risk (RR) associated with each haplotype,
not
only significance testing.
Optional estimation of effects of maternal haplotypes, particularly
relevant in perinatal epidemiology.
The models estimated by Haplin are described in detail in Gjessing
HK
and Lie RT. Case-parent triads: Estimating single- and
double-dose effects of fetal and maternal disease gene haplotypes. Annals of Human Genetics (2006)70,
pp.
382-396. PDF version here.
Also available from Blackwell
Haplin is written by Hakon
K. Gjessing. Hilde-Gunn Bruu contributed to early versions of the
data reading and
preparation
parts.
Rolv Terje Lie has contributed with numerous useful and insightful
suggestions, and inspired the work from its beginning. Øivind
Skare has done extensive testing and simulations with the more recent
versions of Haplin. Please feel free
to contact me at hakon.gjessing@fhi.no,
with
questions or bug reports.
Note: Although we have done our
best to avoid errors, the software is offered without any warranties.
We cannot take responsibility for any problems or damages caused by
using it.
Please: If you use Haplin in
your analyses, it will be much appreciated if you refer to Haplin
(this web page), or better, to the Annals of Human Genetics paper above.
Installation
Haplin is written for use with the statistical software R. However, it
is easy to
install and
requires no previous knowledge of R. R can be downloaded free of charge
from The R Project for Statistical
Computing. For Windows users, a shortcut to the R installation file
is found here.
Haplin
is
implemented as a standard R library, and should run without problems
on all reasonably new R
versions, for Windows, Linux or UNIX.
and save it in a suitable directory. You do not need to unpack it.
Start R and choose the menu Packages >
Install package(s) from local zip files... Select the downloaded
zip file. This will install Haplin in the library section of R.
and save it in a suitable directory. You do not need to unpack it.
Start R and use, for instance, install.packages(repos = NULL, pkgs =
"Haplin_3.0_R_x86_64-pc-linux-gnu.tar.gz")
------
To start using Haplin, use the R command library(Haplin).
Haplin is
then loaded and ready for use.
NOTE: Every time you start a new R session you must load Haplin with the R command library(Haplin). (However, you
do not need to install from
the zip/tar file more
than once.)
NOTE: To S-Plus users: Previous versions of Haplin did also run under
S-Plus, but due to S-Plus's new licencing system I have decided it is
not worth the trouble to maintain an S-Plus version. However, it should
be easy for you to download R and run Haplin very much the same way as
you would under S-Plus.
NOTE: Earlier versions of Haplin were installed by source-ing the files
directly into R, which made installation the same under R and S-Plus.
The current version follows the standard R package installation
procedure.
Running Haplin
Haplin is run by the single command
haplin("C:/work/data.dat")
(or whatever the path to the data file is). The data file (data.dat)
can have any name,
but should be a text file in a specific format (see below). This
command reads data, performs the estimation and prints and plots the
result in one run.
By default, Haplin excludes triads with missing data. To include these
triads in the calculations, include the use.missing argument: haplin("C:/work/data.dat",
use.missing = T)
(The letter "T" is short
for TRUE in R)
For more examples of how to run Haplin, see the haplin help file (in R,
type ?haplin).
The models implemented in Haplin are extensions of the log-linear
models described and developed in the papers
Wilcox AJ, Weinberg CR, Lie RT (1998). Distinguishing the effects of
maternal and offspring genes through studies of "case-parent triads". American Journal of Epidemiology, 148(9): 893-901.
Weinberg CR, Wilcox AJ, Lie RT (1998). A log-linear approach to
case-parent-triad data: assessing effects of disease genes that act
directly or though maternal effects and that may be subject to parental
imprinting. American Journal of
Human Genetics, 62:
969-78
and follow-ups to these. The basic log-linear model for case-parent
triad data allows a user to compute relative risks associated with a
variant allele, together with corresponding confidence intervals and
p-values. It also allows a similar effect estimation for maternal
alleles, i.e. to study the effect of genes of the mother that may influence the
development of the fetus. Haplin extends these models to situations
with multiple densely spaced SNPs (or other markers), where phase is
unknown. Haplin then estimates the relative risks associated with haplotypes,
not only single
markers. In addition, Haplin uses a
parametrization that will detect (at least with sufficient sample size)
dominance- or recessive deviations from a dose-response model. For some
details about parametrization, choice of reference category and
interpretation of results, see parametrization.pdf.
The
most recent Haplin version also includes the option to run on
case-control data, or to combine case-parent triads with control-parent
triads.
(started Apr.
29, 2009)