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Identification of ten loci associated with height highlights new biological pathways in human growth
Open accessAbstract
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 × 10−7 to 8 × 10−22). Together, these 12 loci account for ∼2% of the population variation in height. Individuals with ≤8 height-increasing alleles and ≥16 height-increasing alleles differ in height by ∼3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.
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Citations
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
Combinatorial microRNA target predictions
Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603
XV.—The Correlation between Relatives on the Supposition of Mendelian Inheritance.
Fisher, R. A. (1919) · Transactions of the Royal Society of Edinburgh · doi:10.1017/s0080456800012163 · Cited by 4,387
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Saxena, R., Voight, B. F., Lyssenko, V., Burtt, N. P., de Bakker, P. I. W., Chen, H., Roix, J. J., Kathiresan, S., Hirschhorn, J. N., Daly, M. J., et al. (2007) · Science · doi:10.1126/science.1142358 · Cited by 2,843
Self-citationA genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U., et al. (2007) · Science · doi:10.1126/science.1142382 · Cited by 2,753
Self-citationLohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., & Hirschhorn, J. N. (2003) · Nature Genetics · doi:10.1038/ng1071 · Cited by 1,900
Self-citationScuteri, A., Sanna, S., Chen, W.-M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, M., Usala, G., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030115 · Cited by 1,724
Self-citation
Cited by
Common SNPs explain a large proportion of the heritability for human height
Yang, J., Benyamin, B., McEvoy, B. P., Gordon, S., Henders, A. K., Nyholt, D. R., Madden, P. A., Heath, A. C., Martin, N. G., Montgomery, G. W., et al. (2010) · Nature Genetics · doi:10.1038/ng.608 · Cited by 4,446
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Lango Allen, H., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., Willer, C. J., Jackson, A. U., Vedantam, S., Raychaudhuri, S., et al. (2010) · Nature · doi:10.1038/nature09410 · Cited by 1,945
Self-citationMaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes
Li, Y., Willer, C. J., Ding, J., Scheet, P., & Abecasis, G. R. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20533 · Cited by 1,843
Self-citationPersonal genomes: The case of the missing heritability
Maher, B. (2008) · Nature · doi:10.1038/456018a · Cited by 1,737
the GIANT Consortium (2009) · Nature Genetics · doi:10.1038/ng.287 · Cited by 1,720
MicroRNAs in Stress Signaling and Human Disease
Mendell, J. T., & Olson, E. N. (2012) · Cell · doi:10.1016/j.cell.2012.02.005 · Cited by 1,673
Browning, B. L., & Browning, S. R. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.01.005 · Cited by 1,640
Genes mirror geography within Europe
Novembre, J., Johnson, T., Bryc, K., Kutalik, Z., Boyko, A. R., Auton, A., Indap, A., King, K. S., Bergmann, S., Nelson, M. R., et al. (2008) · Nature · doi:10.1038/nature07331 · Cited by 1,479
Genetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452
Hedgehog: functions and mechanisms
Varjosalo, M., & Taipale, J. (2008) · Genes & Development · doi:10.1101/gad.1693608 · Cited by 1,217
Human genetic variation and its contribution to complex traits
Frazer, K. A., Murray, S. S., Schork, N. J., & Topol, E. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2554 · Cited by 1,073
The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation
Pritchard, J. K., Pickrell, J. K., & Coop, G. (2010) · Current Biology · doi:10.1016/j.cub.2009.11.055 · Cited by 932
Li, Y., Willer, C., Sanna, S., & Abecasis, G. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164242 · Cited by 990
Self-citationGenome-wide association analysis identifies 20 loci that influence adult height
Initiative, D. G., Weedon, M. N., The Wellcome Trust Case Control Consortium, Cambridge GEM Consortium, Lango, H., Lindgren, C. M., Wallace, C., Evans, D. M., Mangino, M., Freathy, R. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.121 · Cited by 826
Park, J.-H., Wacholder, S., Gail, M. H., Peters, U., Jacobs, K. B., Chanock, S. J., & Chatterjee, N. (2010) · Nature Genetics · doi:10.1038/ng.610 · Cited by 678
Self-citationSignals of recent positive selection in a worldwide sample of human populations
Pickrell, J. K., Coop, G., Novembre, J., Kudaravalli, S., Li, J. Z., Absher, D., Srinivasan, B. S., Barsh, G. S., Myers, R. M., Feldman, M. W., et al. (2009) · Genome Research · doi:10.1101/gr.087577.108 · Cited by 717
Practical aspects of imputation-driven meta-analysis of genome-wide association studies
de Bakker, P. I. W., Ferreira, M. A. R., Jia, X., Neale, B. M., Raychaudhuri, S., & Voight, B. F. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn288 · Cited by 531
Self-citationLin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
Hagan, J. P., Piskounova, E., & Gregory, R. I. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1676 · Cited by 491
Rossin, E. J., Lage, K., Raychaudhuri, S., Xavier, R. J., Tatar, D., Benita, Y., Constortium, I. I. B. D. G., Cotsapas, C., & Daly, M. J. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001273 · Cited by 438
Genetic variation in LIN28B is associated with the timing of puberty
Ong, K. K., Elks, C. E., Li, S., Zhao, J. H., Luan, J., Andersen, L. B., Bingham, S. A., Brage, S., Smith, G. D., Ekelund, U., et al. (2009) · Nature Genetics · doi:10.1038/ng.382 · Cited by 366
Measuring missing heritability: Inferring the contribution of common variants
Golan, D., Lander, E. S., & Rosset, S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419064111 · Cited by 288
Epigenetic inheritance and the missing heritability
Trerotola, M., Relli, V., Simeone, P., & Alberti, S. (2015) · Human Genomics · doi:10.1186/s40246-015-0041-3 · Cited by 318
“A significant fraction of height-determining genes has been identified by GWAS analysis [10–12].”
BackgroundAutoimmune diseases: insights from genome-wide association studies
Lettre, G., & Rioux, J. D. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn246 · Cited by 317
Self-citationMeta-analysis of genome-wide association data identifies two loci influencing age at menarche
Perry, J. R. B., Stolk, L., Franceschini, N., Lunetta, K. L., Zhai, G., McArdle, P. F., Smith, A. V., Aspelund, T., Bandinelli, S., Boerwinkle, E., et al. (2009) · Nature Genetics · doi:10.1038/ng.386 · Cited by 294
The neurobiology of individual differences in complex behavioral traits
Hariri, A. R. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135335 · Cited by 273
Swaroop, A., Chew, E. Y., Bowes Rickman, C., & Abecasis, G. R. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164350 · Cited by 270
Self-citationGenome-wide association study identifies sequence variants on 6q21 associated with age at menarche
Sulem, P., Gudbjartsson, D. F., Rafnar, T., Holm, H., Olafsdottir, E. J., Olafsdottir, G. H., Jonsson, T., Alexandersen, P., Feenstra, B., Boyd, H. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.383 · Cited by 219
The genetics of Tourette syndrome: A review
O'Rourke, J. A., Scharf, J. M., Yu, D., & Pauls, D. L. (2009) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2009.06.006 · Cited by 212
“On the other hand, in order to detect alleles with modest effect sizes, tens of thousands of cases and controls could be needed, as demonstrated by studies on human height variation with a combined sample size of ~63,000 individuals [102–104].”
BackgroundLee, Y. T., de Vasconcellos, J. F., Yuan, J., Byrnes, C., Noh, S.-J., Meier, E. R., Kim, K. S., Rabel, A., Kaushal, M., Muljo, S. A., et al. (2013) · Blood · doi:10.1182/blood-2012-12-472308 · Cited by 142
Ghoreishifar, S. M., Eriksson, S., Johansson, A. M., Khansefid, M., Moghaddaszadeh-Ahrabi, S., Parna, N., Davoudi, P., & Javanmard, A. (2020) · Genetics Selection Evolution · doi:10.1186/s12711-020-00571-5 · Cited by 126
Genetic determinants of pubertal timing in the general population
Gajdos, Z. K. Z., Henderson, K. D., Hirschhorn, J. N., & Palmert, M. R. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.038 · Cited by 121
KORSTEN, P., MUELLER, J. C., HERMANNSTÄDTER, C., BOUWMAN, K. M., DINGEMANSE, N. J., DRENT, P. J., LIEDVOGEL, M., MATTHYSEN, E., Van OERS, K., Van OVERVELD, T., et al. (2010) · Molecular Ecology · doi:10.1111/j.1365-294x.2009.04518.x · Cited by 123
He, M., Xu, M., Zhang, B., Liang, J., Chen, P., Lee, J.-Y., Johnson, T. A., Li, H., Yang, X., Dai, J., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddu583 · Cited by 106
Self-citationIV. Growth failure in institutionalized children
Johnson, D. E., & Gunnar, M. R. (2011) · Monographs of the Society for Research in Child Development · doi:10.1111/j.1540-5834.2011.00629.x · Cited by 110
Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers
Perry, G. H., Foll, M., Grenier, J.-C., Patin, E., Nédélec, Y., Pacis, A., Barakatt, M., Gravel, S., Zhou, X., Nsobya, S. L., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402875111 · Cited by 105
A genome-wide association study identifies multiple loci for variation in human ear morphology
Adhikari, K., Reales, G., Smith, A. J. P., Konka, E., Palmen, J., Quinto-Sanchez, M., Acuña-Alonzo, V., Jaramillo, C., Arias, W., Fuentes, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms8500 · Cited by 95
A comparison of approaches to account for uncertainty in analysis of imputed genotypes
Zheng, J., Li, Y., Abecasis, G. R., & Scheet, P. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20552 · Cited by 105
Self-citationDistinct Variants at LIN28B Influence Growth in Height from Birth to Adulthood
Widén, E., Ripatti, S., Cousminer, D. L., Surakka, I., Lappalainen, T., Järvelin, M.-R., Eriksson, J. G., Raitakari, O., Salomaa, V., Sovio, U., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.03.010 · Cited by 88
Self-citationLi, M., Tian, S., Yeung, C. K. L., Meng, X., Tang, Q., Niu, L., Wang, X., Jin, L., Ma, J., Long, K., et al. (2014) · Scientific Reports · doi:10.1038/srep04678 · Cited by 87
Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy
Wu, C., Zhu, X., Liu, W., Ruan, T., & Tao, K. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s139639 · Cited by 82
Indirect evidence for the genetic determination of short stature in African Pygmies
Becker, N. S. A., Verdu, P., Froment, A., Le Bomin, S., Pagezy, H., Bahuchet, S., & Heyer, E. (2011) · American Journal of Physical Anthropology · doi:10.1002/ajpa.21512 · Cited by 64
Heritability of Craniofacial Structures in Normal Subjects and Patients with Sleep Apnea
Chi, L., Comyn, F.-L., Keenan, B. T., Cater, J., Maislin, G., Pack, A. I., & Schwab, R. J. (2014) · Sleep · doi:10.5665/sleep.4082 · Cited by 60
Shriner, D., Adeyemo, A., Gerry, N. P., Herbert, A., Chen, G., Doumatey, A., Huang, H., Zhou, J., Christman, M. F., & Rotimi, C. N. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008398 · Cited by 56
LIN28B in constitutional delay of growth and puberty
Tommiska, J., Wehkalampi, K., Vaaralahti, K., Laitinen, E.-M., Raivio, T., & Dunkel, L. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2344 · Cited by 53
Pemberton, T. J., Verdu, P., Becker, N. S., Willer, C. J., Hewlett, B. S., Le Bomin, S., Froment, A., Rosenberg, N. A., & Heyer, E. (2018) · Human Genetics · doi:10.1007/s00439-018-1902-3 · Cited by 18
Metadata
- Authors
- Initiative, T. D. G., Lettre, G., FUSION, KORA, The Prostate, L. C. A. O. C. S. T., Study, T. N. H., SardiNIA, Jackson, A. U., Gieger, C., Schumacher, F. R., Berndt, S. I., Sanna, S., Eyheramendy, S., Voight, B. F., Butler, J. L., Guiducci, C., Illig, T., Hackett, R., Heid, I. M., Jacobs, K. B., Lyssenko, V., Uda, M., Boehnke, M., Chanock, S. J., Groop, L. C., Hu, F. B., Isomaa, B., Kraft, P., Peltonen, L., Salomaa, V., Schlessinger, D., Hunter, D. J., Hayes, R. B., Abecasis, G. R., Wichmann, H.-E., Mohlke, K. L., & Hirschhorn, J. N.
- Venue
- Nature Genetics
- Published
- 2008-04-06
- Volume
- 40
- Issue
- 5
- Pages
- 584-591
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2140908395
- Cited by
- 588
- References
- 14
- FWCI
- 49.74
- Type
- journal article
- Language
- en
- Open access
- green
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