Question: Help with LD interpretation of clinically relevent SNPs
1
gravatar for jarrodheck
4.6 years ago by
jarrodheck10
jarrodheck10 wrote:

Greetings,

I am trying to interpret the following paragraph from the CPIC: Clinical Pharmacogenetics Implementation Consortium that outlines the LD for the following SNPs:

rs12248560 (*17) and rs4244285 (*2)

The excerpt states that the two SNPs have a D'=1 and an r^2=0.06ish depending on the HapMap population. What confuses me as these two SNPs are well known to exist in isolation. The *17 variant does not always occur in the *2 background, as my interpretation of the excerpt would suggest. Is the CPIC guideline wrong, or am I not understanding something about D' and r^2? Or could there be some population specific effect I am not considering?

"The defining polymorphisms of CYP2C19*2 and *17 are c.681G>A and c.-806C>T, respectively. There is linkage disequilibrium (LD) between c.681G and c.-806T (e.g., |D’|=1.0 and r2=0.064 in CEU HapMap sample; |D’|=1.0 and r2=0.065 in YRI HapMap sample; and |D’|=1.0 and r2=0.074 in CHB HapMap sample). This means that the less common *17 variant (c.-806T) always tracks on the same allele with the more common c.681G. This complicates any interpretation of whether these two variants act independently of one another, and published articles argue both for (29, 35) and against (15, 36, 37) this point."

 

Thanks for any input! :)

Jarrod

ld d' linkage disequilibrium r^2 • 1.2k views
ADD COMMENTlink modified 4.5 years ago by Fabio Marroni2.1k • written 4.6 years ago by jarrodheck10
1
gravatar for Fabio Marroni
4.5 years ago by
Fabio Marroni2.1k
Italy
Fabio Marroni2.1k wrote:

D'=1 probably means that you only see three of the four possible haplotypes. Actually, the excerpt states:

"This means that the less common *17 variant (c.-806T) always tracks on the same allele with the more common c.681G"

So, basically you only see these three haplotypes

c.-806T/c.681G 

c.-806C/c.681G

c.-806C/c.681A  

 

ADD COMMENTlink written 4.5 years ago by Fabio Marroni2.1k
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