{"doi":"10.1371/journal.pgen.1008544","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.","journal":"PLoS Genetics","year":2020,"id":109661,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":523441,"name":"Emil Jørsboe","orcid":"0000-0002-0593-7906","position":1,"is_corresponding":false},{"id":347764,"name":"Line Skotte","orcid":"0000-0002-7398-1271","position":2,"is_corresponding":false},{"id":523442,"name":"Kristian Hanghøj","orcid":"0000-0003-1941-5495","position":3,"is_corresponding":false},{"id":524340,"name":"Camilla H. Sandholt","orcid":null,"position":4,"is_corresponding":false},{"id":11252,"name":"Ida Moltke","orcid":"0000-0001-7052-8554","position":5,"is_corresponding":false},{"id":79391,"name":"Niels Grarup","orcid":"0000-0001-5526-1070","position":6,"is_corresponding":false},{"id":523443,"name":"Timo Kern","orcid":"0000-0001-7139-9766","position":7,"is_corresponding":false},{"id":523444,"name":"Yuvaraj Mahendran","orcid":"0000-0001-5203-6118","position":8,"is_corresponding":false},{"id":524341,"name":"Bolette Søborg","orcid":null,"position":9,"is_corresponding":false},{"id":11249,"name":"Peter Bjerregaard","orcid":"0000-0001-7153-8447","position":10,"is_corresponding":false},{"id":11370,"name":"Christina Viskum Lytken Larsen","orcid":"0000-0002-6245-4222","position":11,"is_corresponding":false},{"id":523445,"name":"Inger Katrine Dahl‐Petersen","orcid":"0000-0002-3157-8847","position":12,"is_corresponding":false},{"id":25027,"name":"Hemant K. Tiwari","orcid":null,"position":13,"is_corresponding":false},{"id":21695,"name":"Bjarke Feenstra","orcid":"0000-0003-1478-649X","position":14,"is_corresponding":false},{"id":523446,"name":"Anders Koch","orcid":"0000-0001-9205-1048","position":15,"is_corresponding":false},{"id":385017,"name":"Howard W. Wiener","orcid":"0009-0009-7071-5531","position":16,"is_corresponding":false},{"id":523447,"name":"Scarlett E. Hopkins","orcid":"0000-0001-5641-7751","position":17,"is_corresponding":false},{"id":16755,"name":"Oluf Pedersen","orcid":"0000-0002-3321-3972","position":18,"is_corresponding":false},{"id":120,"name":"Mads Melbye","orcid":"0000-0001-8264-6785","position":19,"is_corresponding":false},{"id":523448,"name":"Bert B. Boyer","orcid":"0000-0001-5511-4329","position":20,"is_corresponding":false},{"id":11248,"name":"Marit E. 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