Fig. 2: Consequences of genetic architecture for disease mapping.
From: Genetic architecture in Greenland is shaped by demography, structure and selection
a, Mean number of non-causal pLoF variants (± s.e.m.) remaining after removing variants present at MAF > 0.1% in any population in the reference panel (gnomAD v.3.0.0). b, Same as a, but using different MAF thresholds in the reference panel. c, Mean number of tag-SNPs (R2 > 0.8) as a function of distance from focal SNP. d, Number of imputed variants with an INFO score greater than 0.8 and MAF above threshold given on the x axis. Imputation was performed with either the merged reference panel of Greenlandic WGS plus 1KG (n = 448 + 3,202) or only the 1KG reference panel (n = 3,202). e,f, Comparison of largest GWAS in Greenland and Europe on 13 metabolic traits. e, Genome-wide associations explaining more than 1% variance in the largest GWAS across 13 metabolic traits in both Europe and Greenland (95% CI). Gene names are given below bars, with phenotype associated with the variant listed below gene name. For diabetes, we used liability-scale variance explained. Asterisk, the causal gene in this region is uncertain. Chol, total cholesterol; Gluc2h, glucose (2 h); GlucR, glucose (random); HbA1c, haemoglobin 1Ac; HDL, high-density lipoprotein; Trig, triglycerides. f, Mean incr. R2 (±s.e.m.) of European-derived PGS predicting the corresponding 13 metabolic traits normalized to UK Biobank for all Greenland participants, only unadmixed Greenlandic participants or Danish participants. The two bars to the right are the mean incr. R2 after adding the Arctic-specific variants. g, Variance explained for lead SNP in genome-wide significant associations on 175 plasma proteins (Olink) in Greenland and UK Biobank ordered by variance explained and grouped by the model yielding the lowest P value; n = 3,707. The inset shows a zoom-in of the first 20 GWAS hits.
