Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans

Long Lin, Mette K. Andersen, Frederik Filip Stæger, Zilong Li, Kristian Hanghøj, Allan Linneberg, Niels Grarup, Marit Eika Jørgensen, Torben Hansen*, Ida Moltke*, Anders Albrechtsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background: Disease prevalence and mean phenotype values differ between many populations, including Inuit and Europeans. Whether these differences are partly explained by genetic differences or solely due to differences in environmental exposures is still unknown, because estimates of the genetic contribution to these means, which we will here refer to as mean genotypic values, are easily confounded, and because studies across genetically diverse populations are lacking. Methods: Leveraging the unique genetic properties of the small, admixed and historically isolated Greenlandic population, we estimated the differences in mean genotypic value between Inuit and European genetic ancestry using an admixed sibling design. Analyses were performed across 26 metabolic phenotypes, in 1474 admixed sibling pairs present in a cohort of 5996 Greenlanders. Results: After FDR correction for multiple testing, we found significantly lower mean genotypic values in Inuit genetic ancestry compared to European genetic ancestry for body weight (effect size per percentage of Inuit genetic ancestry (se), −0.51 (0.16) kg/%), body mass index (−0.20 (0.06) kg/m2/%), fat percentage (−0.38 (0.13) %/%), waist circumference (−0.42 (0.16) cm/%), hip circumference (−0.38 (0.11) cm/%) and fasting serum insulin levels (−1.07 (0.51) pmol/l/%). The direction of the effects was consistent with the observed mean phenotype differences between Inuit and European genetic ancestry. No difference in mean genotypic value was observed for height, markers of glucose homeostasis, or circulating lipid levels. Conclusions: We show that mean genotypic values for some metabolic phenotypes differ between two human populations using a method not easily confounded by possible differences in environmental exposures. Our study illustrates the importance of performing genetic studies in diverse populations.

Original languageEnglish
Article number71
JournalGenome Medicine
Volume16
Issue number1
ISSN1756-994X
DOIs
Publication statusPublished - Dec 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Admixture
  • Genotypic value
  • Greenlandic population
  • Sibling analysis

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