Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans

PLOS ONE, Sep 2009

There is a large variation in caloric intake and macronutrient preference between individuals and between ethnic groups, and these food intake patterns show a strong heritability. The transition to new food sources during the agriculture revolution around 11,000 years ago probably created selective pressure and shaped the genome of modern humans. One major player in energy homeostasis is the appetite-stimulating hormone neuropeptide Y, in which the stimulatory capacity may be mediated by the neuropeptide Y receptors 1, 2 and 5 (NPY1R, NPY2R and NPY5R). We assess association between variants in the NPY1R, NPY2R and NPY5R genes and nutrient intake in a cross-sectional, single-center study of 400 men aged 40 to 80 years, and we examine whether genomic regions containing these genes show signatures of recent selection in 270 HapMap individuals (90 Africans, 90 Asians, and 90 Caucasians) and in 846 Dutch bloodbank controls. Our results show that derived alleles in NPY1R and NPY5R are associated with lower carbohydrate intake, mainly because of a lower consumption of mono- and disaccharides. We also show that carriers of these derived alleles, on average, consume meals with a lower glycemic index and glycemic load and have higher alcohol consumption. One of these variants shows the hallmark of recent selection in Europe. Our data suggest that lower carbohydrate intake, consuming meals with a low glycemic index and glycemic load, and/or higher alcohol consumption, gave a survival advantage in Europeans since the agricultural revolution. This advantage could lie in overall health benefits, because lower carbohydrate intake, consuming meals with a low GI and GL, and/or higher alcohol consumption, are known to be associated with a lower risk of chronic diseases.

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Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans

et al. (2009) Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans. PLoS ONE 4(9): e7070. doi:10.1371/journal.pone.0007070 Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans Clara C. Elbers 0 Carolien G. F. de Kovel 0 Yvonne T. van der Schouw 0 Juliaan R. Meijboom 0 Florianne 0 Bauer 0 Diederick E. Grobbee 0 Gosia Trynka 0 Jana V. van Vliet-Ostaptchouk 0 Cisca Wijmenga 0 N. Charlotte Onland-Moret 0 Peter Heutink, VU University Medical Center and VU University, the Netherlands 0 1 Complex Genetics Section, Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands, 2 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands, 3 Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, 4 Department of Genetics, University Medical Center Groningen, University of Groningen , Groningen , the Netherlands There is a large variation in caloric intake and macronutrient preference between individuals and between ethnic groups, and these food intake patterns show a strong heritability. The transition to new food sources during the agriculture revolution around 11,000 years ago probably created selective pressure and shaped the genome of modern humans. One major player in energy homeostasis is the appetite-stimulating hormone neuropeptide Y, in which the stimulatory capacity may be mediated by the neuropeptide Y receptors 1, 2 and 5 (NPY1R, NPY2R and NPY5R). We assess association between variants in the NPY1R, NPY2R and NPY5R genes and nutrient intake in a cross-sectional, single-center study of 400 men aged 40 to 80 years, and we examine whether genomic regions containing these genes show signatures of recent selection in 270 HapMap individuals (90 Africans, 90 Asians, and 90 Caucasians) and in 846 Dutch bloodbank controls. Our results show that derived alleles in NPY1R and NPY5R are associated with lower carbohydrate intake, mainly because of a lower consumption of mono- and disaccharides. We also show that carriers of these derived alleles, on average, consume meals with a lower glycemic index and glycemic load and have higher alcohol consumption. One of these variants shows the hallmark of recent selection in Europe. Our data suggest that lower carbohydrate intake, consuming meals with a low glycemic index and glycemic load, and/or higher alcohol consumption, gave a survival advantage in Europeans since the agricultural revolution. This advantage could lie in overall health benefits, because lower carbohydrate intake, consuming meals with a low GI and GL, and/or higher alcohol consumption, are known to be associated with a lower risk of chronic diseases. - Funding: This study was funded by an IOP Genomics grant IGE05012 from SenterNovem. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. One major player in energy homeostasis is the appetitestimulating hormone neuropeptide Y (NPY) [1]. In rodents, NPY evokes eating behavior, inducing particularly carbohydrate intake. Injection of NPY in the brain elicits a strong feeding response even in satiated animals, eventually leading to obesity [2]. The effect of NPY is mediated by the neuropeptide Y receptors (NPYRs) [3]. Especially the Y1, Y2, and Y5 receptors (NPY1R, NPY2R, NPY5R) appear to be candidates for mediating the appetite stimulatory capacity of NPY[4,5] through binding of NPY. These are receptors in the arcuate and paraventricular nuclei of the hypothalamus. Variants in genes coding for these receptors may therefore influence energy intake, which could influence an individuals susceptibility to becoming obese and developing T2D. We have previously pinpointed NPY1R, NPY2R and NPY5R as positional candidate genes for both obesity and T2D [6]. Large variations in caloric intake and macronutrient preference between individuals have been reported and these food intake patterns show a strong heritability [7]. There are also large differences in food intake and percentage of nutrient-specific energy intake among different ethnic groups [8,9]. These ethnic differences in total and nutrient-specific energy intake might be caused by the natural selection of mutations providing an advantage for a particular environment or type of agriculture. The transition to different food sources during the agricultural revolution, which started around 11,000 years ago, was an important selective pressure and the changes in food intake helped shape the genome of modern humans [10]. Genome-wide sequence and SNP data of living humans can be used to study the recent natural selection over t (...truncated)


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Clara C. Elbers, Carolien G. F. de Kovel, Yvonne T. van der Schouw, Juliaan R. Meijboom, Florianne Bauer, Diederick E. Grobbee, Gosia Trynka, Jana V. van Vliet-Ostaptchouk, Cisca Wijmenga, N. Charlotte Onland-Moret. Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans, PLOS ONE, 2009, Volume 4, Issue 9, DOI: 10.1371/journal.pone.0007070