Significant negative heritability in LDSC

Giaco · March 10, 2023, 4:12am

I wondered whether someone could help me understand negative (and significant) h2snp estimates (estimated via either LDSC or stratified LDSC). And if there is some good reference on how to deal with them.

Many thanks!
Giaco

Andrew_Grotzinger · March 10, 2023, 4:50pm

Hi Giaco,

Great question! Raymond Walters previously posted an answer to this on the LDSC github:

github.com/bulik/ldsc

why the estimated heritablity is negative?

opened 05:55AM - 29 Aug 17 UTC

chenyan53535

Hi, I am trying to use your software to calculate the genetic correlation betwee…n phenotype1 and phenotype2, but the estimated heritability of phenotype1 is negative, thus I cannot get the genetic correlation between phenotype1 and phenotype2. why the estimated heritality could be negative? and how to deal with this problem? Thank you. Another question is whether we can calculate the genetic correlation just according to the defination of genetic correlation in your online methods, it is more simple and does not occur the negative heritability? Need your help.

Negative h2SNP estimates are much more common with stratified LDSC due to the greater sampling variation observed for heritability estimates stratified across the functional annotations. I would say if you are seeing a sizable negative h2SNP estimate for LDSC (e.g., < -.3) then it would also be good to look at a manhattan and/or QQ-plot of the hapmap3 SNPs used for LDSC estimation to make sure nothing stands out as potentially off, such as lots of floating points in the manhattan.

Best,
Andrew

luciadehoyos · March 10, 2023, 10:26pm

Hi Andrew,
I was wondering how can this negative heritability be statistically significant?
Thanks!
Lucia