Population genetic differentiation of height and body mass index across Europe

• Published in: Nature genetics Vol. 47; no. 11; pp. 1357 - 1362
• Main Authors: Robinson, Matthew R, Hemani, Gibran, Medina-Gomez, Carolina, Mezzavilla, Massimo, Esko, Tonu, Shakhbazov, Konstantin, Powell, Joseph E, Vinkhuyzen, Anna, Berndt, Sonja I, Gustafsson, Stefan, Justice, Anne E, Kahali, Bratati, Locke, Adam E, Pers, Tune H, Vedantam, Sailaja, Wood, Andrew R, van Rheenen, Wouter, Andreassen, Ole A, Gasparini, Paolo, Metspalu, Andres, Berg, Leonard H van den, Veldink, Jan H, Rivadeneira, Fernando, Werge, Thomas M, Abecasis, Goncalo R, Boomsma, Dorret I, Chasman, Daniel I, de Geus, Eco J C, Frayling, Timothy M, Hirschhorn, Joel N, Hottenga, Jouke Jan, Ingelsson, Erik, Loos, Ruth J F, Magnusson, Patrik K E, Martin, Nicholas G, Montgomery, Grant W, North, Kari E, Pedersen, Nancy L, Spector, Timothy D, Speliotes, Elizabeth K, Goddard, Michael E, Yang, Jian, Visscher, Peter M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2015; Nature Publishing Group
• Subjects: 45; 45/43; 631/208/205/2138; 631/208/457; 692/308/2056; Agriculture; Algorithms; Animal Genetics and Genomics; Biomedical research; Biomedicine; Body Height - genetics; Body Mass Index; Cancer Research; Collaboration; Europe; Funding; Gene Expression Profiling - methods; Gene Expression Profiling - statistics & numerical data; Gene Function; Gene-Environment Interaction; Genetic aspects; Genetic research; Genetic variance; Genetic Variation; Genetics, Population - methods; Genetics, Population - statistics & numerical data; Genome-Wide Association Study - methods; Genome-Wide Association Study - statistics & numerical data; Genomes; Genotype; Geography; Heart; Human Genetics; Humans; Identification and classification; letter; Medical research; Medicin och hälsovetenskap; Models, Genetic; Morphological variation; Phenotype; Polymorphism, Single Nucleotide; Population; Population genetics; Principal Component Analysis; Quantitative genetics; Studies; Europe
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3401

Matthew Robinson and colleagues report an analysis of population genetic differences in human height and body mass index (BMI) across 14 European populations. They estimate the proportion of additive genetic variance attributable to population genetic differences and find evidence for selection increasing height while reducing BMI in European nations. Across-nation differences in the mean values for complex traits are common 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10 −8 ; BMI, P < 5.95 × 10 −4 ), and we find an among-population genetic correlation for tall and slender individuals ( r = −0.80, 95% CI = −0.95, −0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means ( r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI ( P < 0.58).