Question: IBD calculation indicates cryptic relatedness of 1 Individual with all others within a sequencing cohort
2
gravatar for maegsul
11 months ago by
maegsul130
Belgium
maegsul130 wrote:

I know it is not super ideal; but on my WES data of n=~350 individuals I am trying to observe any cryptic relatedness that could be present in the sequencing data. To do so, I first QC my WES data in PLINK with MAF > 0.01 and call rate > 98% filters, leaving ~200K high quality variants for analysis (again, not so ideal for assessing relatedness, but I think it still should give an idea more or less). Then I calculate IBD scores in PLINK with --genome option.

We already identified a first-degree relative pair with this approach (PI-HAT = 0.58, confirmed by fingerprinting [i.e. high similarity between the lengths of STR markers all over the genome, done using stock sample tubes] and clinical files), and new sequencing results indicates another pair (PI-HAT = 0.5). However; interesting thing is that, I have two samples that are somehow related to every other individual in the cohort. I have to indicate that the cohort is consisting of multiple centers all over the Europe, presumably unrelated, so this observation is indeed false-positive.

Sample 1 -> Related to 346 others with 0.25 < PI-HAT < 0.38 scores.
Sample 2 -> Related to 346 others with 0.12 < PI-HAT < 0.22 scores.

All other pairs are having PI-HAT < 0.1.

What could be the reason that we have such an observation? First thing comes to my mind is of course a possible contamination, but I wouldn't expect that since these samples were run in batches of 12, and their libraries were prepared independently as well.

TLDR: In my whole-exome sequencing data, I find one individual with cryptic relatedness to all other 346 participants; what could be the reason?

ibd plink wes relatedness • 535 views
ADD COMMENTlink modified 11 months ago by chrchang5234.9k • written 11 months ago by maegsul130
3
gravatar for chrchang523
11 months ago by
chrchang5234.9k
United States
chrchang5234.9k wrote:

In my experience, this is usually contamination or a similar sequencing problem. I’d recheck the relatedness estimates with plink 2.0 —make-king-table, and then throw out (or resequence if possible) the samples if the pattern remains.

ADD COMMENTlink written 11 months ago by chrchang5234.9k
1

Thank you for your reply! Actually I already checked it with plink2 --make-king-table too and I've got these:

Kinship score between siblings (confirmed) : 0.29

Kinship score between possible new pair: 0.19

Kinship score between Sample1 (with respect to my original post) and all others: varies between ~0.04 and ~0.08

Kinship score between Sample2 (with respect to my original post) and all others: <~0.04

Kinship score between Sample 1 and Sample 2: 0.1682! (I haven't mentioned but this was PI-HAT 0.38 before).

I am not familiar with this KING format; how would you comment on the table? Does it tell anything new? Pattern seems to be remaining.

ADD REPLYlink modified 11 months ago • written 11 months ago by maegsul130
Please log in to add an answer.

Help
Access

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.
Powered by Biostar version 2.3.0
Traffic: 881 users visited in the last hour