title: Greenlandic Inuit show genetic signatures of diet and climate adaptation.
abstract: The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.
authors.affiliation: Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Moltke
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.affiliation: Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Racimo
authors.affiliation: National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Greenland Center for Health Research, University of Greenland, Nuuk, Greenland.
authors.forename: Peter
authors.initials: P
authors.lastname: Bjerregaard
authors.affiliation: National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark. Steno Diabetes Center, 2820 Gentofte, Denmark.
authors.forename: Marit E
authors.initials: ME
authors.lastname: Jørgensen
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark.
authors.forename: Thorfinn S
authors.initials: TS
authors.lastname: Korneliussen
authors.affiliation: Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK. Department of Anthropology, University College London, London WC1H 0BW, UK.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gerbault
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Skotte
authors.affiliation: Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Department of Medicine, Lillebaelt Hospital, Vejle, Denmark.
authors.forename: Cramer
authors.initials: C
authors.lastname: Christensen
authors.affiliation: Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.affiliation: Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Faculty of Medicine, University of Aalborg, Aalborg, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.affiliation: School of Natural Sciences, University of California-Merced, Merced, CA 95343, USA.
authors.forename: Emilia
authors.initials: E
authors.lastname: Huerta-Sánchez
authors.affiliation: Faculty of Medicine, University of Aalborg, Aalborg, Denmark. Department of Cardiology, Aalborg University Hospital, 9100 Aalborg, Denmark.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schmidt
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu.
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.affiliation: Department of Integrative Biology, University of California-Berkeley, Berkeley, CA 94720, USA. Department of Statistics, University of California-Berkeley, Berkeley, CA 94720, USA. torben.hansen@sund.ku.dk albrecht@binf.ku.dk rasmus_nielsen@berkeley.edu.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D000483:Alleles; D001110:Arctic Regions; D001827:Body Height / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002980:Climate; D059305:Diet, High-Fat; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000032:analysis; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006116:Greenland; D006801:Humans; D004930:Inuit / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008563:Membrane Lipids / Q000032:analysis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
chemical_list: D015525:Fatty Acids, Omega-3; D008563:Membrane Lipids