The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: PLOS Genetics, Vol. 16, No. 1, e1008544, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andersen, MK, Jørsboe, E, Skotte, L, Hanghøj, K, Sandholt, CH, Moltke, I, Grarup, N, Kern, T, Mahendran, Y, Søborg, B, Bjerregaard, P, Larsen, CVL, Dahl-Petersen, IK, Tiwari, HK, Feenstra, B, Koch, A, Wiener, HW, Hopkins, SE, Pedersen, O, Melbye, M, Boyer, BB, Jørgensen, ME, Albrechtsen, A & Hansen, T 2020, 'The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders', PLOS Genetics, vol. 16, no. 1, e1008544. https://doi.org/10.1371/journal.pgen.1008544

APA

Andersen, M. K., Jørsboe, E., Skotte, L., Hanghøj, K., Sandholt, C. H., Moltke, I., Grarup, N., Kern, T., Mahendran, Y., Søborg, B., Bjerregaard, P., Larsen, C. V. L., Dahl-Petersen, I. K., Tiwari, H. K., Feenstra, B., Koch, A., Wiener, H. W., Hopkins, S. E., Pedersen, O., ... Hansen, T. (2020). The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders. PLOS Genetics, 16(1), [e1008544]. https://doi.org/10.1371/journal.pgen.1008544

Vancouver

Andersen MK, Jørsboe E, Skotte L, Hanghøj K, Sandholt CH, Moltke I et al. The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders. PLOS Genetics. 2020;16(1). e1008544. https://doi.org/10.1371/journal.pgen.1008544

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. / The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders. In: PLOS Genetics. 2020 ; Vol. 16, No. 1.

Bibtex

@article{70458cefe15444378804f1e1a508e0a0,
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",
abstract = "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/m2 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.",
author = "Andersen, {Mette K.} and Emil J{\o}rsboe and Line Skotte and Kristian Hangh{\o}j and Sandholt, {Camilla H.} and Ida Moltke and Niels Grarup and Timo Kern and Yuvaraj Mahendran and Bolette S{\o}borg and Peter Bjerregaard and Larsen, {Christina V. L.} and Dahl-Petersen, {Inger K.} and Tiwari, {Hemant K.} and Bjarke Feenstra and Anders Koch and Wiener, {Howard W.} and Hopkins, {Scarlett E.} and Oluf Pedersen and Mads Melbye and Boyer, {Bert B.} and J{\o}rgensen, {Marit E.} and Anders Albrechtsen and Torben Hansen",
year = "2020",
doi = "10.1371/journal.pgen.1008544",
language = "English",
volume = "16",
journal = "P L o S Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "1",

}

RIS

TY - JOUR

T1 - The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders

AU - Andersen, Mette K.

AU - Jørsboe, Emil

AU - Skotte, Line

AU - Hanghøj, Kristian

AU - Sandholt, Camilla H.

AU - Moltke, Ida

AU - Grarup, Niels

AU - Kern, Timo

AU - Mahendran, Yuvaraj

AU - Søborg, Bolette

AU - Bjerregaard, Peter

AU - Larsen, Christina V. L.

AU - Dahl-Petersen, Inger K.

AU - Tiwari, Hemant K.

AU - Feenstra, Bjarke

AU - Koch, Anders

AU - Wiener, Howard W.

AU - Hopkins, Scarlett E.

AU - Pedersen, Oluf

AU - Melbye, Mads

AU - Boyer, Bert B.

AU - Jørgensen, Marit E.

AU - Albrechtsen, Anders

AU - Hansen, Torben

PY - 2020

Y1 - 2020

N2 - 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/m2 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.

AB - 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/m2 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.

U2 - 10.1371/journal.pgen.1008544

DO - 10.1371/journal.pgen.1008544

M3 - Journal article

C2 - 31978080

VL - 16

JO - P L o S Genetics

JF - P L o S Genetics

SN - 1553-7390

IS - 1

M1 - e1008544

ER -

ID: 235924743