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The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders
The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biologic...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001991/ https://www.ncbi.nlm.nih.gov/pubmed/31978080 http://dx.doi.org/10.1371/journal.pgen.1008544 |
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author | Andersen, Mette K. Jørsboe, Emil Skotte, Line Hanghøj, Kristian Sandholt, Camilla H. Moltke, Ida Grarup, Niels Kern, Timo Mahendran, Yuvaraj Søborg, Bolette Bjerregaard, Peter Larsen, Christina V. L. Dahl-Petersen, Inger K. Tiwari, Hemant K. Feenstra, Bjarke Koch, Anders Wiener, Howard W. Hopkins, Scarlett E. Pedersen, Oluf Melbye, Mads Boyer, Bert B. Jørgensen, Marit E. Albrechtsen, Anders Hansen, Torben |
author_facet | Andersen, Mette K. Jørsboe, Emil Skotte, Line Hanghøj, Kristian Sandholt, Camilla H. Moltke, Ida Grarup, Niels Kern, Timo Mahendran, Yuvaraj Søborg, Bolette Bjerregaard, Peter Larsen, Christina V. L. Dahl-Petersen, Inger K. Tiwari, Hemant K. Feenstra, Bjarke Koch, Anders Wiener, Howard W. Hopkins, Scarlett E. Pedersen, Oluf Melbye, Mads Boyer, Bert B. Jørgensen, Marit E. Albrechtsen, Anders Hansen, Torben |
author_sort | Andersen, Mette K. |
collection | PubMed |
description | The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup’ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10(-8)), corresponding to 0.64 kg/m(2) lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup’ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.10 SD (0.02), p = 4.7x10(-8)). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; lean mass, -0.84 (0.19) kg; fat mass and percent, -1.66 (0.33) kg and -1.39 (0.27) %; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p<0.0002), lower insulin resistance (HOMA-IR, -0.12 (0.04), p = 0.00021), and favorable lipid levels (triglyceride, -0.05 (0.02) mmol/l, p = 0.025; HDL-cholesterol, 0.04 (0.01) mmol/l, p = 0.0015). In conclusion, we identified a novel variant, where the derived G-allele possibly associated with lower BMI in Arctic populations, and as a consequence also leaner body type, lower insulin resistance, and a favorable lipid profile. |
format | Online Article Text |
id | pubmed-7001991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70019912020-02-18 The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders Andersen, Mette K. Jørsboe, Emil Skotte, Line Hanghøj, Kristian Sandholt, Camilla H. Moltke, Ida Grarup, Niels Kern, Timo Mahendran, Yuvaraj Søborg, Bolette Bjerregaard, Peter Larsen, Christina V. L. Dahl-Petersen, Inger K. Tiwari, Hemant K. Feenstra, Bjarke Koch, Anders Wiener, Howard W. Hopkins, Scarlett E. Pedersen, Oluf Melbye, Mads Boyer, Bert B. Jørgensen, Marit E. Albrechtsen, Anders Hansen, Torben PLoS Genet Research Article The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup’ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10(-8)), corresponding to 0.64 kg/m(2) lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup’ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.10 SD (0.02), p = 4.7x10(-8)). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; lean mass, -0.84 (0.19) kg; fat mass and percent, -1.66 (0.33) kg and -1.39 (0.27) %; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p<0.0002), lower insulin resistance (HOMA-IR, -0.12 (0.04), p = 0.00021), and favorable lipid levels (triglyceride, -0.05 (0.02) mmol/l, p = 0.025; HDL-cholesterol, 0.04 (0.01) mmol/l, p = 0.0015). In conclusion, we identified a novel variant, where the derived G-allele possibly associated with lower BMI in Arctic populations, and as a consequence also leaner body type, lower insulin resistance, and a favorable lipid profile. Public Library of Science 2020-01-24 /pmc/articles/PMC7001991/ /pubmed/31978080 http://dx.doi.org/10.1371/journal.pgen.1008544 Text en © 2020 Andersen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Andersen, Mette K. Jørsboe, Emil Skotte, Line Hanghøj, Kristian Sandholt, Camilla H. Moltke, Ida Grarup, Niels Kern, Timo Mahendran, Yuvaraj Søborg, Bolette Bjerregaard, Peter Larsen, Christina V. L. Dahl-Petersen, Inger K. Tiwari, Hemant K. Feenstra, Bjarke Koch, Anders Wiener, Howard W. Hopkins, Scarlett E. Pedersen, Oluf Melbye, Mads Boyer, Bert B. Jørgensen, Marit E. Albrechtsen, Anders Hansen, Torben The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
title | The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
title_full | The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
title_fullStr | The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
title_full_unstemmed | The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
title_short | The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
title_sort | derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in greenlanders |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001991/ https://www.ncbi.nlm.nih.gov/pubmed/31978080 http://dx.doi.org/10.1371/journal.pgen.1008544 |
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