Home LiteratureArticle Details
PMID: 17559308 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Twin Study

Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci.

PLoS genetics ·Vol. 3 ·No. 6 ·2007-06-00 ·Pages e97

Perola M, Sammalisto S, Hiekkalinna T, Martin NG, Visscher PM, Montgomery GW, Benyamin B, Harris JR, Boomsma D, Willemsen G, Hottenga JJ, Christensen K, Kyvik KO, Sørensen TI, Pedersen NL, Magnusson PK, Spector TD, Widen E, Silventoinen K, Kaprio J, Palotie A, Peltonen L, GenomEUtwin Project

Abstract

Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm).

MeSH Terms
Adult Body Height/genetics Cohort Studies Female Genetic Linkage Genome, Human Humans Lod Score Male Models, Genetic Models, Statistical Twins, Dizygotic/ethnology,genetics Whites
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Perola Markus
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
Sammalisto Sampo
Hiekkalinna Tero
Martin Nick G
Visscher Peter M
Montgomery Grant W
Benyamin Beben
Harris Jennifer R
Boomsma Dorret
Willemsen Gonneke
Hottenga Jouke-Jan
Christensen Kaare
Kyvik Kirsten Ohm
Sørensen Thorkild I A
Pedersen Nancy L
Magnusson Patrik K E
Spector Tim D
Widen Elisabeth
Silventoinen Karri
Kaprio Jaakko
Palotie Aarno
Peltonen Leena
GenomEUtwin Project
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

References (46)
46 references, click to expand
  1. Genetic and environmental factors in complex diseases: the older Finnish Twin Cohort.
    Twin Res. 2002 Oct;5(5):358-65 PMID: 12537859
  2. The St. Thomas' UK Adult Twin Registry.
    Twin Res. 2002 Oct;5(5):440-3 PMID: 12537873
  3. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.
    Nat Genet. 1996 Mar;12(3):241-7 PMID: 8589713
  4. The Swedish Twin Registry in the third millennium.
    Twin Res. 2002 Oct;5(5):427-32 PMID: 12537870
  5. A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature.
    Am J Med Genet. 2002 Nov 15;113(1):29-39 PMID: 12400063
  6. QTLs for height: results of a full genome scan in Dutch sibling pairs.
    Eur J Hum Genet. 2004 Oct;12(10):820-8 PMID: 15305175
  7. Genetic linkage of human height is confirmed to 9q22 and Xq24.
    Hum Genet. 2006 Apr;119(3):295-304 PMID: 16446976
  8. Proceedings: Growth in children with 45XO Turner's syndrome.
    Arch Dis Child. 1974 Oct;49(10):821 PMID: 4429375
  9. Genetic dissection of human stature in a large sample of multiplex pedigrees.
    Ann Hum Genet. 2004 Sep;68(Pt 5):472-88 PMID: 15469424
  10. Empirical evaluation of the genetic similarity of samples from twin registries in Australia and the Netherlands using 359 STRP markers.
    Twin Res Hum Genet. 2006 Aug;9(4):600-2 PMID: 16899170
  11. Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome.
    Nat Genet. 2002 Dec;32(4):661-5 PMID: 12415272
  12. GRR: graphical representation of relationship errors.
    Bioinformatics. 2001 Aug;17(8):742-3 PMID: 11524377
  13. The federated database--a basis for biobank-based post-genome studies, integrating phenome and genome data from 600,000 twin pairs in Europe.
    Eur J Hum Genet. 2007 Jul;15(7):718-23 PMID: 17487219
  14. Bias, precision and heritability of self-reported and clinically measured height in Australian twins.
    Hum Genet. 2006 Nov;120(4):571-80 PMID: 16933140
  15. Linkage analysis of adult height with parent-of-origin effects in the Framingham Heart Study.
    BMC Genet. 2003;4 Suppl 1:S76 PMID: 14975144
  16. Molecular biology of Beckwith-Wiedemann syndrome.
    Med Pediatr Oncol. 1996 Nov;27(5):462-9 PMID: 8827075
  17. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.
    Am J Hum Genet. 2001 Jul;69(1):106-16 PMID: 11410839
  18. Major recessive gene(s) with considerable residual polygenic effect regulating adult height: confirmation of genomewide scan results for chromosomes 6, 9, and 12.
    Am J Hum Genet. 2002 Sep;71(3):646-50 PMID: 12119602
  19. Heritability of adult body height: a comparative study of twin cohorts in eight countries.
    Twin Res. 2003 Oct;6(5):399-408 PMID: 14624724
  20. Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2.
    Am J Med Genet. 1995 Dec 4;59(4):495-500 PMID: 8585571
  21. Netherlands Twin Register: a focus on longitudinal research.
    Twin Res. 2002 Oct;5(5):401-6 PMID: 12537867
  22. Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings.
    PLoS Genet. 2006 Mar;2(3):e41 PMID: 16565746
  23. Quantitative-trait-locus analysis of body-mass index and of stature, by combined analysis of genome scans of five Finnish study groups.
    Am J Hum Genet. 2001 Jul;69(1):117-23 PMID: 11410840
  24. Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population.
    Hum Genet. 2007 Apr;121(2):213-22 PMID: 17180680
  25. Comparison of genome screens for two independent cohorts provides replication of suggestive linkage of bone mineral density to 3p21 and 1p36.
    Am J Hum Genet. 2003 Jan;72(1):144-55 PMID: 12478480
  26. Height discordance in monozygotic females is not attributable to discordant inactivation of X-linked stature determining genes.
    Twin Res. 2001 Feb;4(1):19-24 PMID: 11665320
  27. Linkage analysis of quantitative traits for obesity, diabetes, hypertension, and dyslipidemia on the island of Kosrae, Federated States of Micronesia.
    Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3502-9 PMID: 16537441
  28. Evidence for linkage of stature to chromosome 3p26 in a large U.K. Family data set ascertained for type 2 diabetes.
    Am J Hum Genet. 2002 Feb;70(2):543-6 PMID: 11753821
  29. Merlin--rapid analysis of dense genetic maps using sparse gene flow trees.
    Nat Genet. 2002 Jan;30(1):97-101 PMID: 11731797
  30. PedCheck: a program for identification of genotype incompatibilities in linkage analysis.
    Am J Hum Genet. 1998 Jul;63(1):259-66 PMID: 9634505
  31. Fibroblast growth factor homologous factor 2 (FHF2): gene structure, expression and mapping to the Börjeson-Forssman-Lehmann syndrome region in Xq26 delineated by a duplication breakpoint in a BFLS-like patient.
    Hum Genet. 1999 Jan;104(1):56-63 PMID: 10071193
  32. Data modeling and data communication in GenomEUtwin.
    Twin Res. 2003 Oct;6(5):383-90 PMID: 14624722
  33. The Australian Twin Registry.
    Twin Res. 2002 Oct;5(5):329-36 PMID: 12537854
  34. Loci contributing to adult height and body mass index in African American families ascertained for type 2 diabetes.
    Ann Hum Genet. 2005 Sep;69(Pt 5):517-27 PMID: 16138910
  35. Genomewide scans of complex human diseases: true linkage is hard to find.
    Am J Hum Genet. 2001 Nov;69(5):936-50 PMID: 11565063
  36. Genome scan for body mass index and height in the Framingham Heart Study.
    BMC Genet. 2003;4 Suppl 1:S91 PMID: 14975159
  37. A male-specific quantitative trait locus on 1p21 controlling human stature.
    J Med Genet. 2005 Dec;42(12):932-9 PMID: 15827092
  38. A high-resolution recombination map of the human genome.
    Nat Genet. 2002 Jul;31(3):241-7 PMID: 12053178
  39. AUTOGSCAN: powerful tools for automated genome-wide linkage and linkage disequilibrium analysis.
    Twin Res Hum Genet. 2005 Feb;8(1):16-21 PMID: 15836805
  40. Sex-limited genome-wide linkage scan for body mass index in an unselected sample of 933 Australian twin families.
    Twin Res Hum Genet. 2005 Dec;8(6):616-32 PMID: 16363087
  41. Age-stratified QTL genome scan analyses for anthropometric measures.
    BMC Genet. 2003;4 Suppl 1:S31 PMID: 14975099
  42. Genetic and environmental influences on the tracking of body size from birth to early adulthood.
    Obes Res. 2002 Sep;10(9):875-84 PMID: 12226135
  43. The Danish Twin Registry: 127 birth cohorts of twins.
    Twin Res. 2002 Oct;5(5):352-7 PMID: 12537858
  44. The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations.
    Clin Genet. 2004 Mar;65(3):226-32 PMID: 14756673
  45. Determinants of variation in adult body height.
    J Biosoc Sci. 2003 Apr;35(2):263-85 PMID: 12664962
  46. Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program.
    Eur J Hum Genet. 2003 Mar;11(3):271-4 PMID: 12673281
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0030097
Published
2007-06-00
Epub
2007-00-02
Pages
e97
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1892350
Subset
IM
Databases
OMIM
251260, 301900, 312870
External Links
PubMed source DOI: 10.1371/journal.pgen.0030097 PMC Full Text View journal details
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