Instead of examining markers individually, it can often be more informative to look at a set of
alleles
and markers from the same
chromosome
as a single entity, that is, as a
haplotype
. However, when
genotype
data are collected, the two haplotypes that compose a multilocus genotype are not typically observed. Thus, the alleles, passed together from one parent, for each of the set of markers, remain unknown. The first step in any haplotype analysis is typically to estimate the unobserved haplotype frequencies (
Haplotype Estimation
). Estimates of haplotype frequencies can be used in a variety of ways: to test for multilocus
linkage disequilibrium
, to test for
association
between a
trait
and several markers at once, and to infer the parental haplotypes that an individual receives.
The
Haplotype Trend Regression
process uses information about the
individuals' probabilities for haplotype pairs (the Phase Assignment data set from the
Haplotype Estimation
process), to test for association of each haplotype with a quantitative trait using PROC GLM, a
binary trait
with PROC LOGISTIC, a count trait using PROC GLIMMIX or a survival trait with PROC PHREG.
One data set, the
phase assignment data set
,
is required to run the
Haplotype Trend Regression
process. The
samplegmdata_phase.sas7bdat
data set, shown below
,
was generated using the
Haplotype Estimation
process from data contained in the
samplegmdata.sas7bdat
data set. The
samplegmdata.sas7bdat
data set, described in
Data Sets Used in JMP Genomics Processes
, was computer generated and consists of 1000 rows of individuals with 130 columns corresponding to data on these individuals. The
Individual ID
,
disease
,
Qtrt1
, and
Qtrt2
columns were selected as ID
variables
from the original data set and were included in the
samplegmdata_phase.sas7bdat
data set. Haplotypes, defined by sliding windows encompassing 5 adjacent markers, are listed in a pair of columns. The probability of observing the co-occurrence of a specific pair of haplotypes in an individual is listed. Different haplotype pairs contain the alleles listed in columns
_A_1
through
_A_10
at the five markers in the sliding window.
A second, optional, data set, the
haplotype frequency data set, lists the estimated frequencies for each of the haplotypes for the original data set. These frequencies are used for identifying and combining rare haplotypes if a value greater than
0
is entered for the
Frequency Cutoff for Combining Haplotypes
parameter. The
samplegmdata_hapfreqs.sas7bdat
data set, shown below, was generated from the
samplegmdata.sas7bdat
data set using the
Haplotype Estimation
process.
Both the
samplegmdata_phase.sas7bdat
and s
amplegmdata_hapfreqs.sas7bdat
data sets are contained in the
Sample Data
folder included with JMP Genomics.
For detailed information about the files and data sets used or created by JMP Life Sciences software, see
Files and Data Sets
.
Output from this process is accessed from a
Results
window. Refer to the
Haplotype Trend Regression
output documentation for detailed descriptions and guides to interpreting your results.