Rxivist logo

Reconciling S-LDSC and LDAK models and functional enrichment estimates

By Steven Gazal, Carla Marquez-Luna, Hilary K Finucane, Alkes Price

Posted 30 Jan 2018
bioRxiv DOI: 10.1101/256412

A recent study proposing a new LDAK method (Speed et al. 2017 Nat Genet) reported that functional enrichments (e.g. coding, conserved, regulatory) estimated by LDAK (largest significant enrichment: 2.51x) were much lower than previous estimates obtained using stratified LD score regression (S-LDSC). To investigate this, we developed a method (S-LDSC+LDAK) that combines our S-LDSC method with annotations constructed from LDAK model weights, and determined that this method produced unbiased estimates both in simulations under the S-LDSC model and in simulations under the LDAK model, unlike existing methods. We applied S-LDSC+LDAK to 16 independent UK Biobank traits, and determined that S-LDSC+LDAK enrichment estimates (largest enrichment: 7.51x) were nearly identical to S-LDSC estimates across 28 main annotations. On the other hand, LDAK enrichment estimates (largest enrichment: 3.96x) were substantially lower than S-LDSC estimates (although the discrepancy was smaller than reported by Speed et al., who did not compare the two methods on the same data set). Our results advocate for using S-LDSC in preference to LDAK to infer functional enrichment and confirm the existence of functional annotations that are highly enriched (>>2.51x) for complex trait heritability, providing strong caveats to the LDAK results reported by Speed et al.

Download data

  • Downloaded 1,917 times
  • Download rankings, all-time:
    • Site-wide: 11,129
    • In genetics: 459
  • Year to date:
    • Site-wide: 77,004
  • Since beginning of last month:
    • Site-wide: 118,127

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News