Supplementary Materials

Greenlandic Inuit show genetic signatures of diet and climate adaptation

Matteo Fumagalli, Ida Moltke, Niels Grarup, Fernando Racimo, Peter Bjerregaard, Marit E. Jørgensen, Thorfinn S. Korneliussen, Pascale Gerbault, Line Skotte, Allan Linneberg, Cramer Christensen, Ivan Brandslund, Torben Jørgensen, Emilia Huerta-Sánchez, Erik B. Schmidt, Oluf Pedersen, Torben Hansen, Anders Albrechtsen, Rasmus Nielsen

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

Download Supplement
  • Materials and Methods
  • Supplementary Text
  • Figs. S1 to S14
  • Captions for Tables S1 to S17
Tables S1 to S17
Table S1. Population Branch Statistic (PBS) values for all SNPs in the SNP-chip data set. Minor allele frequencies (MAF) are reported for the overall minor allele for Greenlandic Inuit (GI), East Asians (CHB) and Europeans (CEU)

Table S2. Candidate regions under positive selection in Greenlandic Inuit (GI) based on analyses of the SNP-chip data set.

Table S3. Summary statistics of candidate genes under positive selection based on top PBS entries using either the SNP-chip or the exome sequencing data set. Bold numbers represent values below the 5th percentile of the empirical distribution for Tajima’s D and Fu and Li’s metrics. Genes having less than 2 SNPs, as well as open reading frame entries, were not reported.

Table S4. Population Branch Statistic (PBS) values for all SNPs in the exome-sequencing data set. Non-reference allele frequencies (AF) are reported for Greenlandic Inuit (GI), East Asians (CHB) and Europeans (CEU).

Table S5. Candidate regions under positive selection, based on PBS analysis, in Greenlandic Inuit (GI) using the exome sequencing data set.

Table S6. Significantly enriched gene ontology categories based on the ranking of the maximum PBS score of human genes (P < 0.01, FDR q-value < 0.1, enrichment score > 5).

Table S7. Association test results for top 1 PBS SNP (rs74771917) and 13 metabolic and anthropometric phenotypes in two Greenlandic cohorts (IHIT and B99). The results are based on testing for association using an additive linear mixed model. All the phenotypes were quantile-transformed to a standard normal distribution before they were analyzed. βSD is the estimated effect size for the quantile-transformed data and β is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. The βs are the effects of the derived allele (the major allele in Greenlandic Inuit.)

Table S8. Association test results for top 2 PBS SNP (rs3168072) and 13 metabolic and anthropometric phenotypes in two Greenlandic cohorts (IHIT and B99). The results are based on testing for association using an additive linear mixed model. All the phenotypes were quantile-transformed to a standard normal distribution before they were analyzed. βSD is the estimated effect size for the quantile-transformed data and β is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. The βs are the effects of the derived allele (the major allele in Greenlandic Inuit.)

Table S9. Association test results for top 3 PBS SNP (rs12577276) and 13 metabolic and anthropometric phenotypes in two Greenlandic cohorts (IHIT and B99). The results are based on testing for association using an additive linear mixed model. All the phenotypes were quantile-transformed to a standard normal distribution before they were analyzed. βSD is the estimated effect size for the quantile-transformed data and β is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. The βs are the effects of the derived allele (the major allele in Greenlandic Inuit.)

Table S10. Association test results for top PBS SNP 4 (rs7115739) and 13 metabolic and anthropometric phenotypes in two Greenlandic cohorts (IHIT and B99). For height results for BBH are also shown. The results are based on testing for association using an additive linear mixed model. All the phenotypes were quantile-transformed to a standard normal distribution before they were analyzed. βSD is the estimated effect size for the quantile-transformed data and β is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. The βs are the effects of the derived allele (the major allele in Greenlandic Inuit.)

Table S11. Association test results for top 5 PBS SNP (rs174602) and 13 metabolic and anthropometric phenotypes in two Greenlandic cohorts (IHIT and B99). The results are based on testing for association using an additive linear mixed model. All the phenotypes were quantile-transformed to a standard normal distribution before they were analyzed. βSD is the estimated effect size for the quantile-transformed data and β is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. The βs are the effects of the ancestral allele (the major allele in Greenlandic Inuit.)

Table S12. Association test results for top 6 PBS SNP (rs174570) and 13 metabolic and anthropometric phenotypes in two Greenlandic cohorts (IHIT and B99). For height results for BBH are also shown. The results are based on testing for association using an additive linear mixed model. All the phenotypes were quantile-transformed to a standard normal distribution before they were analyzed. βSD is the estimated effect size for the quantile-transformed data and β is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. The βs are the effects of the ancestral allele (the major allele in Greenlandic Inuit.)

Table S13. Association results between top 6 PBS SNPs and metabolic phenotypes in Europeans. Association analyses in individual cohorts were performed by linear regression combined by a fixed effect meta-analysis (see Supplementary Methods).

Table S14.Results for testing if the effect on weight and height is the same in Greenlandic Inuit and in Europeans for top PBS SNP 4 (rs7115739) and 6 (rs174570). The column "P (M1 vs. M4)" contains the P-values for the tests. "β Inuit” and “β EU” contains ancestry specific effects size estimates measured in units of standard deviation. "Effect Inuit" and "Effect EU" are the estimated ancestry specific effect sizes based on untransformed phenotype values.

Table S15. Association test results for top 4 PBS SNP (rs7115739) and 37 phenotypes related to red blood cell membrane fatty acid composition in the Greenlandic IHIT cohort. The results are based on testing for association using an additive linear mixed model. All phenotypes with less than 20% zero values (corresponding to not measurable) were quantile-transformed to a standard normal distribution before they were analyzed. The rest were transformed to case-control data. βSD is the estimated effect size for the transformed data and b is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. All βs are the effects of the derived allele (the major allele in Greenlandic Inuit).

Table S16. Association test results for top 6 PBS SNP (rs174570) and 37 phenotypes related to red blood cell membrane fatty acid composition in the Greenlandic IHIT cohort. The results are based on testing for association using an additive linear mixed model. All phenotypes with less than 20% zero values (corresponding to not measurable) were quantile-transformed to a standard normal distribution before they were analyzed. The rest were transformed to case-control data. βSD is the estimated effect size for the transformed data and b is the effect size estimated for the untransformed data. P-values below 0.05 are marked in red. All βs are the effects of the derived allele (the major allele in Greenlandic Inuit).

Table S17. eQTLs with FDR < 5% from European RNA-seq data (from the Geuvadis exon database). Significant SNPs with high PBS in the FADS region are reported. Highlighted in red are eQTLs with -log10 p-values > 10.