The second heritability estimation approach was DZ-only heritability following a constrained ACE mixed model approach for full siblings. 84 For this approach, a REML mixed model was used to relate the observed variation in true IBD proportions among DZ pairs to the expression phenotypes. P-values were obtained using likelihood ratio tests. The third approach was heritability estimated from the genetic relatedness matrix, as implemented in GCTA. 46 For this approach, we divided the NTR subjects into unrelated sets (twin set 1, n=1370, twin set 2, n=1372), and averaged the h2 estimates from the two twin sets. The results showed almost no correlation with twin-based heritability (not shown), and we reasoned that genome-wide IBD might have reduced power for those genes influenced largely locally. Thus we ran GCTA again, using IBD estimation performed in the local region within ±1Mb of each transcript.
