Celiac genetic testing results - help

[Caterina0909]

 

Hi all

 

I received the results above - it was a genetic test for celiac. The result 'risk allele' - does anyone know what that means?

 

Thanks

 

Catherine 

[RMJ]

I’m surprised it was presented this way, but here goes an attempt at an explanation.

When doing genetic testing, tests often look at SNPs, or single nucleotide polymorphisms.  This means instead of determining the DNA sequence of the entire gene, nucleotide by nucleotide,  they just look at the single nucleotide spots that commonly vary from person to person.  Most DNA is exactly the same in each human so this makes testing much simpler.

The rs numbers in the “marker” column are the positions on the DNA that were evaluated. The ones listed are six positions which are associated with celiac disease.

The letters in the “genotype” column are the DNA nucleotides found at those positions.

”Zygosity” refers to the fact that everyone has two copies of each gene, or two alleles, one from each parent. Homozygous means the two copies are the same, heterozygous means the two copies are different.

On one SNP you are heterozygous for a risk allele; you have one copy of one of the three possible risk alleles for the HLA DQ 2.2 version of the HLA gene, a gene involved in the immune system.  Because it is a risk allele, it does not mean that you will definitely get celiac disease, but you have a risk for celiac disease.  Even if someone has two copies of each risk allele for HLA DQ 2.2, risk alleles have what is called incomplete penetrance - the trait of celiac disease isn’t expressed in everyone with HLA DQ 2.2.

Please let me know if there is anything I said that doesn’t make sense!

 

[Caterina0909]

42 minutes ago, RMJ said:

I’m surprised it was presented this way, but here goes an attempt at an explanation.

When doing genetic testing, tests often look at SNPs, or single nucleotide polymorphisms.  This means instead of determining the DNA sequence of the entire gene, nucleotide by nucleotide,  they just look at the single nucleotide spots that commonly vary from person to person.  Most DNA is exactly the same in each human so this makes testing much simpler.

The rs numbers in the “marker” column are the positions on the DNA that were evaluated. The ones listed are six positions which are associated with celiac disease.

The letters in the “genotype” column are the DNA nucleotides found at those positions.

”Zygosity” refers to the fact that everyone has two copies of each gene, or two alleles, one from each parent. Homozygous means the two copies are the same, heterozygous means the two copies are different.

On one SNP you are heterozygous for a risk allele; you have one copy of one of the three possible risk alleles for the HLA DQ 2.2 version of the HLA gene, a gene involved in the immune system.  Because it is a risk allele, it does not mean that you will definitely get celiac disease, but you have a risk for celiac disease.  Even if someone has two copies of each risk allele for HLA DQ 2.2, risk alleles have what is called incomplete penetrance - the trait of celiac disease isn’t expressed in everyone with HLA DQ 2.2.

Please let me know if there is anything I said that doesn’t make sense!

 

That is a wonderful explanation. Thank-you. Would I have to have more than one risk allele to develop celiac disease? 
 

 

Just now, Caterina0909 said:

That is a wonderful explanation. Thank-you. Would I have to have more than one risk allele to develop celiac disease? 
 

 

Sorry… I should say, more than one Marker with a risk allele

[RMJ]

I just went and looked at the scientific journal article that describes all of this and I may have misled you a bit. I’m a scientist but not a geneticist!   It looks like with just one copy of DQ 2.2 you don’t have a risk for celiac disease.  You would also need a copy of DQ 2.5 or DQ7.  So in your case having DQ 2.2, you would need another marker to develop celiac disease, according to this article.

See the Table 1, and the legend to Figure 1.

Article on celiac risk alleles

[Caterina0909]

8 minutes ago, RMJ said:

I just went and looked at the scientific journal article that describes all of this and I may have misled you a bit. I’m a scientist but not a geneticist!   It looks like with just one copy of DQ 2.2 you don’t have a risk for celiac disease.  You would also need a copy of DQ 2.5 or DQ7.  So in your case having DQ 2.2, you would need another marker to develop celiac disease, according to this article.

See the Table 1, and the legend to Figure 1.

Article on celiac risk alleles

That’s a really helpful article. Thank-you. Can I bother you once more to ask if you know if the paragraph below applies to me? I am without the DQ2.5 and DQ8 gene but have half the DQ2.2 molecule? 

[RMJ]

I think it would, so maybe you do have some risk. I do find parts of the article and part of Table 1 confusing, like the number of copies.  The HLA molecule has multiple subunits which I think is confusing me.  I don’t know where they got the “genetic risk” scores.  I’ll see if I can find a reference for that.

[Caterina0909]

7 minutes ago, RMJ said:

I think it would, so maybe you do have some risk. I do find parts of the article and part of Table 1 confusing, like the number of copies.  The HLA molecule has multiple subunits which I think is confusing me.  I don’t know where they got the “genetic risk” scores.  I’ll see if I can find a reference for that.

You are a star. Honestly, thank-you so much for taking the time to reply. 

[RMJ]

Here is the abstract of a more recent paper (2020) that concludes in the discussion that your results would mean you are not at risk.  Looks like the debate is ongoing!

Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease

[Caterina0909]

12 hours ago, RMJ said:

Here is the abstract of a more recent paper (2020) that concludes in the discussion that your results would mean you are not at risk.  Looks like the debate is ongoing!

Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease

Thanks - this is really interesting. I am so convinced I have celiac disease but not getting too far with a diagnosis.