The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders
| العنوان: | The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders |
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| المؤلفون: | Marit E. Jørgensen, Bjarke Feenstra, Anders Koch, Camilla H. Sandholt, Mads Melbye, Yuvaraj Mahendran, Scarlett E. Hopkins, Oluf Pedersen, Anders Albrechtsen, Howard W. Wiener, Timo Kern, Peter Bjerregaard, Hemant K. Tiwari, Torben Hansen, Mette K. Andersen, Ida Moltke, Line Skotte, Inger Katrine Dahl-Petersen, Christina Viskum Lytken Larsen, Niels Grarup, Bolette Søborg, Kristian Hanghøj, Bert B. Boyer, Emil Jørsboe |
| المصدر: | PLoS Genetics, Vol 16, Iss 1, p e1008544 (2020) 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, Melbye, M, Boyer, B B, Jørgensen, M E, 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, pp. e1008544 . https://doi.org/10.1371/journal.pgen.1008544 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, Melbye, M, Boyer, B B, Jørgensen, M E, 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 PLoS Genetics |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Cancer Research, Physiology, Greenland, Adipose tissue, QH426-470, Biochemistry, Body Mass Index, Geographical Locations, Fats, Endocrinology, Mathematical and Statistical Techniques, 0302 clinical medicine, Medicine and Health Sciences, Genetics (clinical), Adiposity, 2. Zero hunger, 0303 health sciences, education.field_of_study, Statistics, Metaanalysis, Lipids, Europe, Cholesterol, Physiological Parameters, Inuit, Physical Sciences, Metabolome, Population study, DNA, Intergenic, Female, Waist Circumference, Research Article, medicine.medical_specialty, Population, Biology, Research and Analysis Methods, Polymorphism, Single Nucleotide, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Genetics, Humans, Obesity, Statistical Methods, Allele, education, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Endocrine Physiology, Chromosomes, Human, Pair 11, Body Weight, Biology and Life Sciences, medicine.disease, United States, Genetic Loci, People and Places, North America, Lean body mass, Insulin Resistance, Body mass index, Mathematics, Alaska, 030217 neurology & neurosurgery |
| الوصف: | 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 Author summary The risk of developing obesity is strongly affected by lifestyle, particularly diet and level of physical activity, but also by genetic predisposition. Knowledge about the genes predisposing to obesity can inform about biological processes underlying this condition, and possibly identify targets for obesity treatment. In the present study, we take advantage of the genetic architecture of the Greenlandic population to identify genetic variants associated with alterations in body-mass index, as a measure of obesity. By examining more than 100,000 genetic variants in 4,626 Greenlanders we identify a specific variant, rs4936356, where the derived G-allele was associated with lower body-mass index, lower insulin resistance, and favorable lipid levels. We verified the association with body-mass index in a combined analysis including two additional Arctic cohorts. These results contribute to the understanding of the genetic predisposition to obesity, however, further studies are required to replicate these findings and to identify the gene through which the rs4936356 variant is affecting body-mass index. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1553-7404 1553-7390 |
| DOI: | 10.1371/journal.pgen.1008544 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa70a42c65e7dcc6c2748ac8d4992940 https://doaj.org/article/31a1e3c4b2684f3ca2c1fe7ceb71c161 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fa70a42c65e7dcc6c2748ac8d4992940 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537404 15537390 |
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| DOI: | 10.1371/journal.pgen.1008544 |