Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans
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Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans. / Lin, Long; Andersen, Mette K.; Stæger, Frederik Filip; Li, Zilong; Hanghøj, Kristian; Linneberg, Allan; Grarup, Niels; Jørgensen, Marit Eika; Hansen, Torben; Moltke, Ida; Albrechtsen, Anders.
In: Genome Medicine, Vol. 16, 71, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans
AU - Lin, Long
AU - Andersen, Mette K.
AU - Stæger, Frederik Filip
AU - Li, Zilong
AU - Hanghøj, Kristian
AU - Linneberg, Allan
AU - Grarup, Niels
AU - Jørgensen, Marit Eika
AU - Hansen, Torben
AU - Moltke, Ida
AU - Albrechtsen, Anders
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Admixture
KW - Genotypic value
KW - Greenlandic population
KW - Sibling analysis
U2 - 10.1186/s13073-024-01326-3
DO - 10.1186/s13073-024-01326-3
M3 - Journal article
C2 - 38778393
AN - SCOPUS:85194017149
VL - 16
JO - Genome Medicine
JF - Genome Medicine
SN - 1756-994X
M1 - 71
ER -
ID: 393465239