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
. 2012 Apr 15;44(5):532-538.
doi: 10.1038/ng.2238.

Common variants at 12q15 and 12q24 are associated with infant head circumference

H Rob Taal #  1   2   3 , Beate St Pourcain #  4 , Elisabeth Thiering #  5 , Shikta Das #  6 , Dennis O Mook-Kanamori #  1   2   3   7 , Nicole M Warrington  8   9 , Marika Kaakinen  10   11 , Eskil Kreiner-Møller  12 , Jonathan P Bradfield  13 , Rachel M Freathy  14 , Frank Geller  15 , Mònica Guxens  16   17   18 , Diana L Cousminer  19 , Marjan Kerkhof  20 , Nicholas J Timpson  4 , M Arfan Ikram  1   21 , Lawrence J Beilin  22 , Klaus Bønnelykke  12 , Jessica L Buxton  23 , Pimphen Charoen  6   24 , Bo Lund Krogsgaard Chawes  12 , Johan Eriksson  25   26   27 , David M Evans  4 , Albert Hofman  1   3 , John P Kemp  4 , Cecilia E Kim  13 , Norman Klopp  28   29 , Jari Lahti  30 , Stephen J Lye  9 , George McMahon  4 , Frank D Mentch  13 , Martina Müller  31   32   33 , Paul F O'Reilly  34 , Inga Prokopenko  35   36 , Fernando Rivadeneira  1   37 , Eric A P Steegers  38 , Jordi Sunyer  16   17   18   39 , Carla Tiesler  5   40 , Hanieh Yaghootkar  14 ; Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium; Monique M B Breteler  1 , Stephanie Debette  41 , Myriam Fornage  42 , Vilmundur Gudnason  43   44 , Lenore J Launer  45 , Aad van der Lugt  21 , Thomas H Mosley  46 , Sudha Seshadri  41 , Albert V Smith  43   44 , Meike W Vernooij  1   21 ; Early Genetics & Lifecourse Epidemiology (EAGLE) consortium; Alexandra If Blakemore  23 , Rosetta M Chiavacci  13 , Bjarke Feenstra  15 , Julio Fernandez-Benet  47 , Struan F A Grant  13   48   49 , Anna-Liisa Hartikainen  50 , Albert J van der Heijden  2 , Carmen Iñiguez  18   51 , Mark Lathrop  52   53 , Wendy L McArdle  54 , Anne Mølgaard  12 , John P Newnham  8 , Lyle J Palmer  9   55 , Aarno Palotie  19   56   57   58 , Annneli Pouta  59 , Susan M Ring  54 , Ulla Sovio  6   60 , Marie Standl  5 , Andre G Uitterlinden  1   37 , H-Erich Wichmann  5   31   33 , Nadja Hawwa Vissing  12 , Charles DeCarli  61 , Cornelia M van Duijn  1 , Mark I McCarthy  35   36   62 , Gerard H Koppelman  63 , Xavier Estivill  18   39   64 , Andrew T Hattersley  65 , Mads Melbye  15 , Hans Bisgaard  12 , Craig E Pennell  8 , Elisabeth Widen  19 , Hakon Hakonarson  13   48   49 , George Davey Smith  4 , Joachim Heinrich  5 , Marjo-Riitta Jarvelin  10   59   66 ; Early Growth Genetics (EGG) Consortium; Vincent W V Jaddoe  1   2   3
Collaborators, Affiliations

Common variants at 12q15 and 12q24 are associated with infant head circumference

H Rob Taal et al. Nat Genet. .

Erratum in

  • Nat Genet. 2013 June;45(6):713. Sørensen, Thorkild I A [removed]

Abstract

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Directly genotyped and imputed SNPs are plotted using filled circles with their meta-analysis P values (as −log10 values) as a function of genomic position (NCBI Build 36). In each plot, the discovery-stage SNP taken forward to replication stage is represented by a purple diamond (defining a global meta-analysis P value). Local LD structure is reflected by the plotted estimated recombination rates (taken from HapMap) in the region around the associated SNPs and their correlated proxies. The correlations of the lead SNP to other SNPs at the locus are shown on a color scale from r2<0.2 dark blue; 0.2=<r2<0.4 light-blue; 0.4=<r2<0.6 green; 0.6=<r2<0.8 orange; r2>=0.8 red. Superimposed on the plot are the recombination rates (light blue line, second y axis). Gene annotations are shown as the dark blue arrows. The regional plots were drawn using the LocusZoom software. 1a Regional plot of locus 12q24.31 1b Regional plot of locus 12q15 1c Regional association plot of locus 17q21.1; downstream of the lead signal, rs9915547 is indicated (r2 0.22 HapMap CEU with rs11655470), which showed a genome wide significant association with adult intra cranial volume (P=1.5×10−12) as described in Ikram et al.
Figure 1
Figure 1
Directly genotyped and imputed SNPs are plotted using filled circles with their meta-analysis P values (as −log10 values) as a function of genomic position (NCBI Build 36). In each plot, the discovery-stage SNP taken forward to replication stage is represented by a purple diamond (defining a global meta-analysis P value). Local LD structure is reflected by the plotted estimated recombination rates (taken from HapMap) in the region around the associated SNPs and their correlated proxies. The correlations of the lead SNP to other SNPs at the locus are shown on a color scale from r2<0.2 dark blue; 0.2=<r2<0.4 light-blue; 0.4=<r2<0.6 green; 0.6=<r2<0.8 orange; r2>=0.8 red. Superimposed on the plot are the recombination rates (light blue line, second y axis). Gene annotations are shown as the dark blue arrows. The regional plots were drawn using the LocusZoom software. 1a Regional plot of locus 12q24.31 1b Regional plot of locus 12q15 1c Regional association plot of locus 17q21.1; downstream of the lead signal, rs9915547 is indicated (r2 0.22 HapMap CEU with rs11655470), which showed a genome wide significant association with adult intra cranial volume (P=1.5×10−12) as described in Ikram et al.
Figure 1
Figure 1
Directly genotyped and imputed SNPs are plotted using filled circles with their meta-analysis P values (as −log10 values) as a function of genomic position (NCBI Build 36). In each plot, the discovery-stage SNP taken forward to replication stage is represented by a purple diamond (defining a global meta-analysis P value). Local LD structure is reflected by the plotted estimated recombination rates (taken from HapMap) in the region around the associated SNPs and their correlated proxies. The correlations of the lead SNP to other SNPs at the locus are shown on a color scale from r2<0.2 dark blue; 0.2=<r2<0.4 light-blue; 0.4=<r2<0.6 green; 0.6=<r2<0.8 orange; r2>=0.8 red. Superimposed on the plot are the recombination rates (light blue line, second y axis). Gene annotations are shown as the dark blue arrows. The regional plots were drawn using the LocusZoom software. 1a Regional plot of locus 12q24.31 1b Regional plot of locus 12q15 1c Regional association plot of locus 17q21.1; downstream of the lead signal, rs9915547 is indicated (r2 0.22 HapMap CEU with rs11655470), which showed a genome wide significant association with adult intra cranial volume (P=1.5×10−12) as described in Ikram et al.
See this image and copyright information in PMC

Similar articles

  • Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility.
    Veluchamy A, Hébert HL, van Zuydam NR, Pearson ER, Campbell A, Hayward C, Meng W, McCarthy MI, Bennett DLH, Palmer CNA, Smith BH. Veluchamy A, et al. JAMA Netw Open. 2021 Dec 1;4(12):e2136560. doi: 10.1001/jamanetworkopen.2021.36560. JAMA Netw Open. 2021. PMID: 34854908 Free PMC article.
  • A Genome-Wide Association Study Identifies the Association between the 12q24 Locus and Black Tea Consumption in Japanese Populations.
    Furukawa K, Igarashi M, Jia H, Nogawa S, Kawafune K, Hachiya T, Takahashi S, Saito K, Kato H. Furukawa K, et al. Nutrients. 2020 Oct 18;12(10):3182. doi: 10.3390/nu12103182. Nutrients. 2020. PMID: 33080986 Free PMC article.
  • Common variants at 12q14 and 12q24 are associated with hippocampal volume.
    Bis JC, DeCarli C, Smith AV, van der Lijn F, Crivello F, Fornage M, Debette S, Shulman JM, Schmidt H, Srikanth V, Schuur M, Yu L, Choi SH, Sigurdsson S, Verhaaren BF, DeStefano AL, Lambert JC, Jack CR Jr, Struchalin M, Stankovich J, Ibrahim-Verbaas CA, Fleischman D, Zijdenbos A, den Heijer T, Mazoyer B, Coker LH, Enzinger C, Danoy P, Amin N, Arfanakis K, van Buchem MA, de Bruijn RF, Beiser A, Dufouil C, Huang J, Cavalieri M, Thomson R, Niessen WJ, Chibnik LB, Gislason GK, Hofman A, Pikula A, Amouyel P, Freeman KB, Phan TG, Oostra BA, Stein JL, Medland SE, Vasquez AA, Hibar DP, Wright MJ, Franke B, Martin NG, Thompson PM; Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium; Nalls MA, Uitterlinden AG, Au R, Elbaz A, Beare RJ, van Swieten JC, Lopez OL, Harris TB, Chouraki V, Breteler MM, De Jager PL, Becker JT, Vernooij MW, Knopman D, Fazekas F, Wolf PA, van der Lugt A, Gudnason V, Longstreth WT Jr, Brown MA, Bennett DA, van Duijn CM, Mosley TH, Schmidt R, Tzourio C, Launer LJ, Ikram MA, Seshadri S; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Bis JC, et al. Nat Genet. 2012 Apr 15;44(5):545-51. doi: 10.1038/ng.2237. Nat Genet. 2012. PMID: 22504421 Free PMC article.
  • Common variants at 6q22 and 17q21 are associated with intracranial volume.
    Ikram MA, Fornage M, Smith AV, Seshadri S, Schmidt R, Debette S, Vrooman HA, Sigurdsson S, Ropele S, Taal HR, Mook-Kanamori DO, Coker LH, Longstreth WT Jr, Niessen WJ, DeStefano AL, Beiser A, Zijdenbos AP, Struchalin M, Jack CR Jr, Rivadeneira F, Uitterlinden AG, Knopman DS, Hartikainen AL, Pennell CE, Thiering E, Steegers EA, Hakonarson H, Heinrich J, Palmer LJ, Jarvelin MR, McCarthy MI, Grant SF, St Pourcain B, Timpson NJ, Smith GD, Sovio U; Early Growth Genetics Consortium; Nalls MA, Au R, Hofman A, Gudnason H, van der Lugt A, Harris TB, Meeks WM, Vernooij MW, van Buchem MA, Catellier D, Jaddoe VW, Gudnason V, Windham BG, Wolf PA, van Duijn CM, Mosley TH Jr, Schmidt H, Launer LJ, Breteler MM, DeCarli C; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Ikram MA, et al. Nat Genet. 2012 Apr 15;44(5):539-44. doi: 10.1038/ng.2245. Nat Genet. 2012. PMID: 22504418 Free PMC article.
  • Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
    Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BE, Breteler MM, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PT, van Duijn CM, Kao L, Cheng CY, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T; Global BPgen Consortium; Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FM, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TY. Ikram MK, et al. PLoS Genet. 2010 Oct 28;6(10):e1001184. doi: 10.1371/journal.pgen.1001184. PLoS Genet. 2010. PMID: 21060863 Free PMC article.
See all similar articles

Cited by

  • Investigation of genetic determinants of cognitive change in later life.
    Mahedy L, Anderson EL, Tilling K, Thornton ZA, Elmore AR, Szalma S, Simen A, Culp M, Zicha S, Harel BT, Davey Smith G, Smith EN, Paternoster L. Mahedy L, et al. Transl Psychiatry. 2024 Jan 18;14(1):31. doi: 10.1038/s41398-023-02726-6. Transl Psychiatry. 2024. PMID: 38238328 Free PMC article.
  • Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.
    Goovaerts S, Hoskens H, Eller RJ, Herrick N, Musolf AM, Justice CM, Yuan M, Naqvi S, Lee MK, Vandermeulen D, Szabo-Rogers HL, Romitti PA, Boyadjiev SA, Marazita ML, Shaffer JR, Shriver MD, Wysocka J, Walsh S, Weinberg SM, Claes P. Goovaerts S, et al. Nat Commun. 2023 Nov 16;14(1):7436. doi: 10.1038/s41467-023-43237-8. Nat Commun. 2023. PMID: 37973980 Free PMC article. Review.
  • Cohort Profile Update: Project Viva mothers.
    Rifas-Shiman SL, Aris IM, Switkowski KM, Young J, Fleisch AF, James-Todd T, Zota AR, Perng W, Hivert MF, Rich-Edwards JW, Perez Capotosto M, Chavarro JE, Oken E. Rifas-Shiman SL, et al. Int J Epidemiol. 2023 Dec 25;52(6):e332-e339. doi: 10.1093/ije/dyad137. Int J Epidemiol. 2023. PMID: 37875013 No abstract available.
  • Genomic insights into the genetic basis of eagle-beak jaw, large head, and long tail in the big-headed turtle.
    Gong S, Ge Y, Wei Y, Gao Y. Gong S, et al. Ecol Evol. 2023 Jul 25;13(7):e10361. doi: 10.1002/ece3.10361. eCollection 2023 Jul. Ecol Evol. 2023. PMID: 37502307 Free PMC article.
  • Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.
    Medina-Gomez C, Mullin BH, Chesi A, Prijatelj V, Kemp JP, Shochat-Carvalho C, Trajanoska K, Wang C, Joro R, Evans TE, Schraut KE, Li-Gao R, Ahluwalia TS, Zillikens MC, Zhu K, Mook-Kanamori DO, Evans DS, Nethander M, Knol MJ, Thorleifsson G, Prokic I, Zemel B, Broer L, McGuigan FE, van Schoor NM, Reppe S, Pawlak MA, Ralston SH, van der Velde N, Lorentzon M, Stefansson K, Adams HHH, Wilson SG, Ikram MA, Walsh JP, Lakka TA, Gautvik KM, Wilson JF, Orwoll ES, van Duijn CM, Bønnelykke K, Uitterlinden AG, Styrkársdóttir U, Akesson KE, Spector TD, Tobias JH, Ohlsson C, Felix JF, Bisgaard H, Grant SFA, Richards JB, Evans DM, van der Eerden B, van de Peppel J, Ackert-Bicknell C, Karasik D, Kague E, Rivadeneira F. Medina-Gomez C, et al. Commun Biol. 2023 Jul 4;6(1):691. doi: 10.1038/s42003-023-04869-0. Commun Biol. 2023. PMID: 37402774 Free PMC article.
See all "Cited by" articles

References

    1. Lango Allen H, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–8. - PMC - PubMed
    1. Ikram MA, et al. Common variants at 6q22 and 17q21 are associated with intracranial volume. Nat Genet. 2012 advance online publication. - PMC - PubMed
    1. Simon-Sanchez J, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet. 2009;41:1308–12. - PMC - PubMed
    1. International Parkinson Disease Genomics, C et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377:641–9. - PMC - PubMed
    1. Webb A, et al. Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. Arch Neurol. 2008;65:1473–8. - PMC - PubMed

Publication types

Substances