Hello,

If you have individual data, you can use plink (version 1.047) or BEAGLE to infer haplotypes and do association tests with your case/control status.

Best

Fabienne

Thanks but i will appreiate if you give me link of this program

You can easily find them with a search for the software names on the web :

http://zzz.bwh.harvard.edu/plink/

https://faculty.washington.edu/browning/beagle/b3.html

What about haploview?

How can I use haploview to calculate haplotyptes and the link of this software if possible?

Hi Rami,

Please see attached the instructions and an example input file I wrote a decade ago for Haploview input file generation:

1) PDF file: Instructions for generating Haploview input files

2) XLS file: an example of raw data and input files (check out all tabs)

I hope this helps.

Best,

Naser

Thanks for your response naser

I have one problem 

After i enter my data everything is ok i can calculate allelic frequencies but for haplotypes no data appear just blank background

Can you help me ? Thanks

Hi Rami,

This is because you have to select your "block" in the LD display. Select the SNPs by dragging your mouse and a black triangular black border appears. Go to the haplotype tab next and you'll see your haplotypes.

Best,

Naser

Thanks naser 

Last issue 

I use case control study. When i enter data in affection status

Do i enter both cases and controls or each group alone?

Hi Rami,

You must enter all data together (case + control). Otherwise it won't recognise the case-control design of your data. That is why you have the affection status where controls are 1 and cases are 2.

Hope it helps.

Naser

Thanks alot naser

Hi Rami,

I recommend that you calculate from first principles, fishing using computer programmes can lead to confounding relationships in data. I hope the following is helpful, especially adjusting for multiple degrees of freedom, Bonferroni and for population equilibrium, Hardy Weinberg. The distance of separation between the alleles is also an important indicator. If the data is to be published then these statistical tests should be included.

The frequency of the alleles and genotypes in both subgroups and controls can be compared for significance with one sided testing, using contingency tables and chi-squared test with Yates correction where appropriate. P values of

Hi Naser Ansari-Pour

I have a question regarding Haploview , in case-control study looking for association with disease X, how you could know whether the SNPs are tagging or not by using Haploview?

Hi Hamdan Zaki Hamdan ,

You can use Tagger implemented within Haploview.

When you load your SNP data, a tab for Tagger becomes available and you can set the threshold for tagging correlation (default is good; R2>=0.8).

Hope it helps

Naser

Hi Naser Ansari-Pour Many thanks for your prompt response, yes it was very helpful. What about the value of r2 found in the LD Blocks between two SNPs along with LOD and D' ? what does it indicate? can I use it instead of running a tagging test?

One further question, which is more accurate in describing LD, D' or LOD? and if I have D'=1 and LOD=2 how can Interpretate these?

For tagging, use the formal test by running Tagger and not based on the LD plot.

For LD, I suggest D'. R2 would be useful if both SNPs are frequent.

As a rule of thumb:

1) D'=1 tells you there is no recombination as you will have 3 haplotypes

2) R2>0.8 suggests that you can omit one of the two SNPs because you can predict the genotype of one SNP from the other, thus not providing independent data/association.

Dear Naser Ansari-Pour

Many thanks again for your response, can you advise how to do the tagging test? cause I use aggresive tagging option using two marker haplotypes, it just show me that both SNPs are captured 2 of 2alleles at r2=0.8mean max r2 is 1. What you think??

I will be grateful if you share with me a guide for interpretation of D' , r2, DOL ,,

Do pairwise tagging. If you pick one SNP by another, one of the two SNPs is redundant (tagged by another).

There is already a lot of discussion on LD measures in Researchgate such as

https://www.researchgate.net/post/I_have_Linkage_Disequilibrium_LD_data_for_two_SNPs-r2_is_about_014_D_is_around_08_Could_these_SNPs_be_said_to_be_in_strong_LD

All the best

Naser Ansari-Pour

I did every thing as in the PDF file but when I submitted the excel files the answer was "File formatting error" what is the solution?

Hi Haidar Abdulamir ,

As mentioned in the instructions, you have to paste the input into a text editor (e.g. notepad) to create text files for Haploview to read (not Excel files).

Best wishes

Hi,

How is calculated below haplotype associations for 4 SNPs?

Could you explain the results /values, please?

Thanks

Block Haplotype Freq. Case, Control Ratio Counts Case,Control Frequencies Chi Square P Value

Block 1

TGGG 0.620 46.4 : 29.6, 51.6 : 30.4 0.611, 0.629 0.056 0.8131

CCGG 0.189 15.4 : 60.6, 14.4 : 67.6 0.202, 0.176 0.179 0.672

Below is a table comparing 6 variations of the IL12B gene in HCV patients. I have attached my paper and suggest you speek to a medical statistician at the university.

TABLE III. Percentage Frequency of Haplotypes of IL-12B

(1188A/C) 30 UTR Polymorphism (AC), IL-12B 4 bp

Insertion/Deletion Intron 4 Polymorphism (EF) and IL-12B

4 bp Insertion/Deletion Promoter Polymorphism (1/2)

Haplotype RNA positive RNA negative Controls

“A”-“1” 66.7% (45) 50.0% (22) 44.8% (30)

“A”-“2” 33.3% (29) 32.2% (19) 49.2% (33)

“C”-“1” 0.0% (0) 6.7% (6) 3.0% (2)

“C”-“2” 0.0% (0) 11.1% (8) 3.0% (2)

“A”-“F” 77.5% (138) 73.3% (66) 85.7% (84)

“A”-“E” 10.1% (18) 12.2% (11) 4.4% (4)

“C”-“F” 5.6% (10) 6.7% (6) 5.5% (5)

“C”-“E” 6.8% (12) 7.8% (7) 5.5% (5)

“1”-“F” 47.5% (38) 37.7% (20) 40.2% (37)

“1”-“E” 10% (8) 11.3% (6) 3.3% (3)

“2”-“F” 28.8% (23) 34.0% (18) 47.8% (44)

“2”-“E” 13.7% (11) 17.0% (9) 8.7% (8)

The number of subjects is given in parentheses. “A”.A allele in IL-

12B gene (1188A/C) polymorphic site, “C”.C allele in IL-12B gene

(1188A/C) polymorphic site, 1.4 bp deletion on IL-12B promoter

region, 2.4 bp insertion on IL-12B promoter region, F.4bp

insertion on IL-12B intron 4 region, E.4 bp deletion on IL-12B

intron 4 region.

After Bonferroni correction for 12 degrees of freedom (n1.11)

there were no significant Pc differences between any of the

haplotypes.