Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2011 Oct;7(10):e1002298.
doi: 10.1371/journal.pgen.1002298. Epub 2011 Oct 6.

Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry

Amidou N'Diaye  1 , Gary K Chen, Cameron D Palmer, Bing Ge, Bamidele Tayo, Rasika A Mathias, Jingzhong Ding, Michael A Nalls, Adebowale Adeyemo, Véronique Adoue, Christine B Ambrosone, Larry Atwood, Elisa V Bandera, Lewis C Becker, Sonja I Berndt, Leslie Bernstein, William J Blot, Eric Boerwinkle, Angela Britton, Graham Casey, Stephen J Chanock, Ellen Demerath, Sandra L Deming, W Ryan Diver, Caroline Fox, Tamara B Harris, Dena G Hernandez, Jennifer J Hu, Sue A Ingles, Esther M John, Craig Johnson, Brendan Keating, Rick A Kittles, Laurence N Kolonel, Stephen B Kritchevsky, Loic Le Marchand, Kurt Lohman, Jiankang Liu, Robert C Millikan, Adam Murphy, Solomon Musani, Christine Neslund-Dudas, Kari E North, Sarah Nyante, Adesola Ogunniyi, Elaine A Ostrander, George Papanicolaou, Sanjay Patel, Curtis A Pettaway, Michael F Press, Susan Redline, Jorge L Rodriguez-Gil, Charles Rotimi, Benjamin A Rybicki, Babatunde Salako, Pamela J Schreiner, Lisa B Signorello, Andrew B Singleton, Janet L Stanford, Alex H Stram, Daniel O Stram, Sara S Strom, Bhoom Suktitipat, Michael J Thun, John S Witte, Lisa R Yanek, Regina G Ziegler, Wei Zheng, Xiaofeng Zhu, Joseph M Zmuda, Alan B Zonderman, Michele K Evans, Yongmei Liu, Diane M Becker, Richard S Cooper, Tomi Pastinen, Brian E Henderson, Joel N Hirschhorn, Guillaume Lettre, Christopher A Haiman
Affiliations
Meta-Analysis

Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry

Amidou N'Diaye et al. PLoS Genet. 2011 Oct.

Erratum in

  • PLoS Genet. 2011 Nov;7(11). doi:10.1371/annotation/58c67154-3f10-4155-9085-dcd6e3689008

Abstract

Adult height is a classic polygenic trait of high heritability (h(2) approximately 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10(-12) and 2p14-rs4315565, P = 1.2×10(-8)). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10(-4) for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Quantile–quantile (QQ) plot of the meta-analysis with up to 3.3 M SNPs across 9 studies (N = 20,427).
Each black circle represents an observed statistic for genotyped SNPs only (defined as the −log10 P) against the corresponding expected statistic. The grey area corresponds to the 90% confidence intervals calculated empirically using permutations. The individual studies' inflation factors, as well as the inflation factor of the meta-analysis, were corrected using genomic control. The inflation factor of the meta-analysis is λGC = 1.064.
Figure 2
Figure 2. SNPs are plotted using LocusZoom by position on the chromosome against association with adult height (−log10 P).
The SNP name shown on the plot was the most significant SNP after the discovery meta-analysis. Estimated recombination rates (from HapMap) are plotted in cyan to reflect the local LD structure. The SNPs surrounding the most significant SNP are color coded to reflect their LD with this SNP (taken from pairwise r 2 values from the ARIC African Americans Affymetrix6.0 dataset for rs1239627 (A) and from the HapMap YRI data for rs4315565 (B)). The size of the points on the plots is proportional to the number of individuals with available genotype for any given SNP. Genes, the position of exons and the direction of transcription from the UCSC genome browser are noted. Hashmarks represent SNP positions available in the meta-analysis.
Figure 3
Figure 3. Height association results.
In Europeans from the GIANT Consortium (A) and in individuals of African ancestry (B) (this study) at the LCORL locus on chromosome 4. The GIANT Consortium originally reported SNP rs6449353, whereas rs7663818 was fine-mapped in the African height meta-analysis. For each panel, the light blue box corresponds to the chromosomal interval flanked by the leftmost and rightmost SNPs with a r 2≥0.8 with rs7663818 in HapMap CEU (A) and YRI (B) participants: these intervals are 250 kb and 80 kb wide in CEU and YRI, respectively.
See this image and copyright information in PMC

Similar articles

  • Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe).
    Carty CL, Johnson NA, Hutter CM, Reiner AP, Peters U, Tang H, Kooperberg C. Carty CL, et al. Hum Mol Genet. 2012 Feb 1;21(3):711-20. doi: 10.1093/hmg/ddr489. Epub 2011 Oct 21. Hum Mol Genet. 2012. PMID: 22021425 Free PMC article.
  • Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.
    Graff M, Justice AE, Young KL, Marouli E, Zhang X, Fine RS, Lim E, Buchanan V, Rand K, Feitosa MF, Wojczynski MK, Yanek LR, Shao Y, Rohde R, Adeyemo AA, Aldrich MC, Allison MA, Ambrosone CB, Ambs S, Amos C, Arnett DK, Atwood L, Bandera EV, Bartz T, Becker DM, Berndt SI, Bernstein L, Bielak LF, Blot WJ, Bottinger EP, Bowden DW, Bradfield JP, Brody JA, Broeckel U, Burke G, Cade BE, Cai Q, Caporaso N, Carlson C, Carpten J, Casey G, Chanock SJ, Chen G, Chen M, Chen YI, Chen WM, Chesi A, Chiang CWK, Chu L, Coetzee GA, Conti DV, Cooper RS, Cushman M, Demerath E, Deming SL, Dimitrov L, Ding J, Diver WR, Duan Q, Evans MK, Falusi AG, Faul JD, Fornage M, Fox C, Freedman BI, Garcia M, Gillanders EM, Goodman P, Gottesman O, Grant SFA, Guo X, Hakonarson H, Haritunians T, Harris TB, Harris CC, Henderson BE, Hennis A, Hernandez DG, Hirschhorn JN, McNeill LH, Howard TD, Howard B, Hsing AW, Hsu YH, Hu JJ, Huff CD, Huo D, Ingles SA, Irvin MR, John EM, Johnson KC, Jordan JM, Kabagambe EK, Kang SJ, Kardia SL, Keating BJ, Kittles RA, Klein EA, Kolb S, Kolonel LN, Kooperberg C, Kuller L, Kutlar A, Lange L, Langefeld CD, Le Marchand L, Leonard H, Lettre G, Levin AM, Li Y, Li J, Liu Y, Liu Y, Liu S, Lohm… See abstract for full author list ➔ Graff M, et al. Am J Hum Genet. 2021 Apr 1;108(4):564-582. doi: 10.1016/j.ajhg.2021.02.011. Epub 2021 Mar 12. Am J Hum Genet. 2021. PMID: 33713608 Free PMC article.
  • Fine-mapping in African Americans of 8 recently discovered genetic loci for plasma lipids: the Jackson Heart Study.
    Keebler ME, Deo RC, Surti A, Konieczkowski D, Guiducci C, Burtt N, Buxbaum SG, Sarpong DF, Steffes MW, Wilson JG, Taylor HA, Kathiresan S. Keebler ME, et al. Circ Cardiovasc Genet. 2010 Aug;3(4):358-64. doi: 10.1161/CIRCGENETICS.109.914267. Epub 2010 Jun 22. Circ Cardiovasc Genet. 2010. PMID: 20570916 Free PMC article.
  • Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development.
    Chan Y, Salem RM, Hsu YH, McMahon G, Pers TH, Vedantam S, Esko T, Guo MH, Lim ET; GIANT Consortium; Franke L, Smith GD, Strachan DP, Hirschhorn JN. Chan Y, et al. Am J Hum Genet. 2015 May 7;96(5):695-708. doi: 10.1016/j.ajhg.2015.02.018. Epub 2015 Apr 9. Am J Hum Genet. 2015. PMID: 25865494 Free PMC article.
  • Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.
    Lanktree MB, Guo Y, Murtaza M, Glessner JT, Bailey SD, Onland-Moret NC, Lettre G, Ongen H, Rajagopalan R, Johnson T, Shen H, Nelson CP, Klopp N, Baumert J, Padmanabhan S, Pankratz N, Pankow JS, Shah S, Taylor K, Barnard J, Peters BJ, Maloney CM, Lobmeyer MT, Stanton A, Zafarmand MH, Romaine SP, Mehta A, van Iperen EP, Gong Y, Price TS, Smith EN, Kim CE, Li YR, Asselbergs FW, Atwood LD, Bailey KM, Bhatt D, Bauer F, Behr ER, Bhangale T, Boer JM, Boehm BO, Bradfield JP, Brown M, Braund PS, Burton PR, Carty C, Chandrupatla HR, Chen W, Connell J, Dalgeorgou C, Boer Ad, Drenos F, Elbers CC, Fang JC, Fox CS, Frackelton EC, Fuchs B, Furlong CE, Gibson Q, Gieger C, Goel A, Grobbee DE, Hastie C, Howard PJ, Huang GH, Johnson WC, Li Q, Kleber ME, Klein BE, Klein R, Kooperberg C, Ky B, Lacroix A, Lanken P, Lathrop M, Li M, Marshall V, Melander O, Mentch FD, Meyer NJ, Monda KL, Montpetit A, Murugesan G, Nakayama K, Nondahl D, Onipinla A, Rafelt S, Newhouse SJ, Otieno FG, Patel SR, Putt ME, Rodriguez S, Safa RN, Sawyer DB, Schreiner PJ, Simpson C, Sivapalaratnam S, Srinivasan SR, Suver C, Swergold G, Sweitzer NK, Thomas KA, Thorand B, Timpson NJ, Tischfield S, Tobin M, Tomaszewski M, Verschuren … See abstract for full author list ➔ Lanktree MB, et al. Am J Hum Genet. 2011 Jan 7;88(1):6-18. doi: 10.1016/j.ajhg.2010.11.007. Epub 2010 Dec 30. Am J Hum Genet. 2011. PMID: 21194676 Free PMC article.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Perola M, Sammalisto S, Hiekkalinna T, Martin NG, Visscher PM, et al. Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci. PLoS Genet. 2007;3:e97. doi: 10.1371/journal.pgen.0030097. - DOI - PMC - PubMed
    1. Visscher PM, Medland SE, Ferreira MA, Morley KI, Zhu G, et al. Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings. PLoS Genet. 2006;2:e41. doi: 10.1371/journal.pgen.0020041. - DOI - PMC - PubMed
    1. Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–838. - PMC - PubMed
    1. Fisher RA. The Correlation Between Relatives on the Supposition of Mendelian Inheritance. Transactions of the Royal Society of Edinburgh. 1918;52:399–433.
    1. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet. 2009;41:527–534. - PubMed

Publication types

Grants and funding