BACKGROUND: Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. OBJECTIVE: To perform a genome-wide screen for loci affecting adult stature by combined analysis of four previously performed genome-wide scans. METHODS: We developed a web based computer tool, Cartographer, for combining genetic marker maps which positions genetic markers accurately using the July 2003 release of the human genome sequence and the deCODE genetic map. Using Cartographer, we combined the primary genotype data from four genome-wide scans and performed variance components (VC) linkage analyses for human stature on the pooled dataset of 1417 individuals from 277 families and performed VC analyses for males and females separately. RESULTS: We found significant linkage to stature on 1p21 (multipoint LOD score 4.25) and suggestive linkages on 9p24 and 18q21 (multipoint LOD scores 2.57 and 2.39, respectively) in males-only analyses. We also found suggestive linkage to 4q35 and 22q13 (multipoint LOD scores 2.18 and 2.85, respectively) when we analysed both females and males and to 13q12 (multipoint LOD score 2.66) in females-only analyses. CONCLUSIONS: We strengthened the evidence for linkage to previously reported quantitative trait loci (QTL) for stature and also found significant evidence of a novel male-specific QTL on 1p21. Further investigation of several interesting candidate genes in this region will help towards characterisation of this first sex-specific locus affecting human stature.
BACKGROUND: Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. OBJECTIVE: To perform a genome-wide screen for loci affecting adult stature by combined analysis of four previously performed genome-wide scans. METHODS: We developed a web based computer tool, Cartographer, for combining genetic marker maps which positions genetic markers accurately using the July 2003 release of the human genome sequence and the deCODE genetic map. Using Cartographer, we combined the primary genotype data from four genome-wide scans and performed variance components (VC) linkage analyses for human stature on the pooled dataset of 1417 individuals from 277 families and performed VC analyses for males and females separately. RESULTS: We found significant linkage to stature on 1p21 (multipoint LOD score 4.25) and suggestive linkages on 9p24 and 18q21 (multipoint LOD scores 2.57 and 2.39, respectively) in males-only analyses. We also found suggestive linkage to 4q35 and 22q13 (multipoint LOD scores 2.18 and 2.85, respectively) when we analysed both females and males and to 13q12 (multipoint LOD score 2.66) in females-only analyses. CONCLUSIONS: We strengthened the evidence for linkage to previously reported quantitative trait loci (QTL) for stature and also found significant evidence of a novel male-specific QTL on 1p21. Further investigation of several interesting candidate genes in this region will help towards characterisation of this first sex-specific locus affecting human stature.
Authors: V C Sheffield; J L Weber; K H Buetow; J C Murray; D A Even; K Wiles; J M Gastier; J C Pulido; C Yandava; S L Sunden Journal: Hum Mol Genet Date: 1995-10 Impact factor: 6.150
Authors: M M Mahtani; E Widén; M Lehto; J Thomas; M McCarthy; J Brayer; B Bryant; G Chan; M Daly; C Forsblom; T Kanninen; A Kirby; L Kruglyak; K Munnelly; M Parkkonen; M P Reeve-Daly; A Weaver; T Brettin; G Duyk; E S Lander; L C Groop Journal: Nat Genet Date: 1996-09 Impact factor: 38.330
Authors: Y Li; D A Lacerda; M L Warman; D R Beier; H Yoshioka; Y Ninomiya; J T Oxford; N P Morris; K Andrikopoulos; F Ramirez Journal: Cell Date: 1995-02-10 Impact factor: 41.582
Authors: Karolina Aberg; Guangyun Sun; Diane Smelser; Subba Rao Indugula; Hui-Ju Tsai; Matthew S Steele; John Tuitele; Ranjan Deka; Stephen T McGarvey; Daniel E Weeks Journal: Hum Biol Date: 2008-04 Impact factor: 0.553
Authors: Peter M Visscher; Stuart Macgregor; Beben Benyamin; Gu Zhu; Scott Gordon; Sarah Medland; William G Hill; Jouke-Jan Hottenga; Gonneke Willemsen; Dorret I Boomsma; Yao-Zhong Liu; Hong-Wen Deng; Grant W Montgomery; Nicholas G Martin Journal: Am J Hum Genet Date: 2007-10-01 Impact factor: 11.025
Authors: Sampo Sammalisto; Tero Hiekkalinna; Karen Schwander; Sharon Kardia; Alan B Weder; Beatriz L Rodriguez; Alessandro Doria; Jennifer A Kelly; Gail R Bruner; John B Harley; Susan Redline; Emma K Larkin; Sanjay R Patel; Amy J H Ewan; James L Weber; Markus Perola; Leena Peltonen Journal: Eur J Hum Genet Date: 2008-09-10 Impact factor: 4.246
Authors: Tatiana I Axenovich; I V Zorkoltseva; N M Belonogova; M V Struchalin; A V Kirichenko; M Kayser; B A Oostra; C M van Duijn; Y S Aulchenko Journal: Hum Genet Date: 2009-05-24 Impact factor: 4.132
Authors: J Kettunen; M Perola; N G Martin; B K Cornes; S G Wilson; G W Montgomery; B Benyamin; J R Harris; D Boomsma; G Willemsen; J-J Hottenga; P E Slagboom; K Christensen; K O Kyvik; T I A Sørensen; N L Pedersen; P K E Magnusson; T Andrew; T D Spector; E Widen; K Silventoinen; J Kaprio; A Palotie; L Peltonen Journal: Int J Obes (Lond) Date: 2009-09-01 Impact factor: 5.095