Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height
Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn,Cecilia M. Lindgren,Cecilia M. Lindgren,Mark J. Daly,Andrew Kirby,Stephen F. Schaffner,Noël P. Burtt,David Altshuler,David Altshuler,Alex Parker,John D. Rioux,Jill Platko,Daniel Gaudet,Thomas J. Hudson,Thomas J. Hudson,Leif Groop,Eric S. Lander +18 more
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TLDR
Strong supporting evidence is obtained for linkage to the region on chromosome 7, and studies suggest that highly heritable complex traits such as stature may be genetically tractable and provide insight into the genetic architecture of complex traits.Abstract:
Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide P<.06), 7q31.3-36 (LOD 3.40 at marker D7S2195 in Sweden, P<.02), 12p11.2-q14 (LOD 3.35 at markers D12S10990-D12S398 in Finland, P<.05) and 13q32-33 (LOD 3.56 at markers D13S779-D13S797 in Finland, P<.05). In a companion article (Perola et al. 2001 [in this issue]), strong supporting evidence is obtained for linkage to the region on chromosome 7. These studies suggest that highly heritable complex traits such as stature may be genetically tractable and provide insight into the genetic architecture of complex traits.read more
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Genome-wide association studies: theoretical and practical concerns
TL;DR: The main factors — including models of the allelic architecture of common diseases, sample size, map density and sample-collection biases — that need to be taken into account in order to optimize the cost efficiency of identifying genuine disease-susceptibility loci are outlined.
Journal ArticleDOI
Heritability of Adult Body Height: A Comparative Study of Twin Cohorts in Eight Countries
Karri Silventoinen,Sampo Sammalisto,Markus Perola,Dorret I. Boomsma,Belinda K. Cornes,Chayna J. Davis,Leo Dunkel,Marlies de Lange,Jennifer R. Harris,Jacob v. B. Hjelmborg,Michelle Luciano,Nicholas G. Martin,Jakob Mortensen,Lorenza Nisticò,Nancy L. Pedersen,Axel Skytthe,Tim D. Spector,Maria Antonietta Stazi,Gonneke Willemsen,Jaakko Kaprio +19 more
TL;DR: The results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.
Journal ArticleDOI
Identification of ten loci associated with height highlights new biological pathways in human growth.
Guillaume Lettre,Guillaume Lettre,Anne U. Jackson,Christian Gieger,Fredrick R. Schumacher,Fredrick R. Schumacher,Sonja I. Berndt,Serena Sanna,Susana Eyheramendy,Benjamin F. Voight,Benjamin F. Voight,Johannah L. Butler,Candace Guiducci,Thomas Illig,Rachel Hackett,Iris M. Heid,Kevin B. Jacobs,Valeriya Lyssenko,Manuela Uda,Michael Boehnke,Stephen J. Chanock,Leif Groop,Leif Groop,Frank B. Hu,Frank B. Hu,Bo Isomaa,Peter Kraft,Leena Peltonen,Leena Peltonen,Leena Peltonen,Veikko Salomaa,David Schlessinger,David J. Hunter,Richard B. Hayes,Gonçalo R. Abecasis,H-Erich Wichmann,Karen L. Mohlke,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn +39 more
TL;DR: A meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs found 10 newly identified and two previously reported loci were strongly associated with variation in height, and highlight several pathways as important regulators of human stature.
Journal ArticleDOI
Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study
Ronald H. Gray,Xianbin Li,Godfrey Kigozi,David Serwadda,Heena Brahmbhatt,Fred Wabwire-Mangen,Fred Nalugoda,Mohamed Kiddugavu,Nelson K. Sewankambo,Thomas C. Quinn,Thomas C. Quinn,Steven J. Reynolds,Steven J. Reynolds,Maria J. Wawer +13 more
TL;DR: The risk of HIV acquisition rises during pregnancy, unlikely to be due to sexual risk behaviours, but might be attributable to hormonal changes affecting the genital tract mucosa or immune responses.
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Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites.
S. Ferrari,Samuel Deutsch,Urmila Choudhury,Urmila Choudhury,Thierry Chevalley,Jean-Philippe Bonjour,Emmanouil T. Dermitzakis,René Rizzoli,Stylianos E. Antonarakis +8 more
TL;DR: It is suggested that LRP5 variants significantly contribute to LS-bone-mass and size determination in men by influencing vertebral bone growth during childhood.
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Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.
John D. Rioux,Mark S. Silverberg,Mark J. Daly,A. Hillary Steinhart,Robin S. McLeod,Anne M. Griffiths,Todd Green,Thomas Brettin,Valerie Stone,Shelley B. Bull,Alain Bitton,C. Noel Williams,Gordon R. Greenberg,Zane Cohen,Eric S. Lander,Thomas J. Hudson,Thomas J. Hudson,Katherine A. Siminovitch +17 more
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