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

Markus Perola, Sampo Sammalisto, Tero Hiekkalinna, Nick G Martin, Peter M Visscher, Grant W Montgomery, Beben Benyamin, Jennifer R Harris, Dorret I Boomsma, Gonneke Willemsen, Jouke-Jan Hottenga, Kaare Christensen, Kirsten Ohm Kyvik, Thorkild I. A Sørensen, Nancy L Pedersen, Patrik K. E Magnusson, Tim D Spector, Elisabeth Widen, Karri Silventoinen, Jaakko KaprioAarno Palotie, Leena Peltonen, GenomEUtwin Project

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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 tencentimorgan 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).
Alkuperäiskielienglanti
LehtiPLoS Genetics
Vuosikerta3
Numero6
ISSN1553-7390
DOI - pysyväislinkit
TilaJulkaistu - 2007
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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  • 314 Terveystieteet

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Perola, Markus ; Sammalisto, Sampo ; Hiekkalinna, Tero ; Martin, Nick G ; Visscher, Peter M ; Montgomery, Grant W ; Benyamin, Beben ; Harris, Jennifer R ; Boomsma, Dorret I ; 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. / Combined genome scans for body stature in 6,602 European twins : evidence for common Caucasian loci. Julkaisussa: PLoS Genetics. 2007 ; Vuosikerta 3, Nro 6.
@article{4bb938ea7bd544a296d9be5a1dd6813f,
title = "Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci",
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 tencentimorgan 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).",
keywords = "314 Health sciences",
author = "Markus Perola and Sampo Sammalisto and Tero Hiekkalinna and Martin, {Nick G} and Visscher, {Peter M} and Montgomery, {Grant W} and Beben Benyamin and Harris, {Jennifer R} and Boomsma, {Dorret I} and Gonneke Willemsen and Jouke-Jan Hottenga and Kaare Christensen and Kyvik, {Kirsten Ohm} and S{\o}rensen, {Thorkild I. A} and Pedersen, {Nancy L} and Magnusson, {Patrik K. E} and Spector, {Tim D} and Elisabeth Widen and Karri Silventoinen and Jaakko Kaprio and Aarno Palotie and Leena Peltonen and {GenomEUtwin Project}",
year = "2007",
doi = "10.1371/journal.pgen.0030097",
language = "English",
volume = "3",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "PUBLIC LIBRARY OF SCIENCE",
number = "6",

}

Perola, M, Sammalisto, S, Hiekkalinna, T, Martin, NG, Visscher, PM, Montgomery, GW, Benyamin, B, Harris, JR, Boomsma, DI, Willemsen, G, Hottenga, J-J, Christensen, K, Kyvik, KO, Sørensen, TIA, Pedersen, NL, Magnusson, PKE, Spector, TD, Widen, E, Silventoinen, K, Kaprio, J, Palotie, A, Peltonen, L & GenomEUtwin Project 2007, 'Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci', PLoS Genetics, Vuosikerta 3, Nro 6. https://doi.org/10.1371/journal.pgen.0030097

Combined genome scans for body stature in 6,602 European twins : evidence for common Caucasian loci. / Perola, Markus; Sammalisto, Sampo; Hiekkalinna, Tero; Martin, Nick G; Visscher, Peter M; Montgomery, Grant W; Benyamin, Beben; Harris, Jennifer R; Boomsma, Dorret I; 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.

julkaisussa: PLoS Genetics, Vuosikerta 3, Nro 6, 2007.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Combined genome scans for body stature in 6,602 European twins

T2 - evidence for common Caucasian loci

AU - Perola, Markus

AU - Sammalisto, Sampo

AU - Hiekkalinna, Tero

AU - Martin, Nick G

AU - Visscher, Peter M

AU - Montgomery, Grant W

AU - Benyamin, Beben

AU - Harris, Jennifer R

AU - Boomsma, Dorret I

AU - Willemsen, Gonneke

AU - Hottenga, Jouke-Jan

AU - Christensen, Kaare

AU - Kyvik, Kirsten Ohm

AU - Sørensen, Thorkild I. A

AU - Pedersen, Nancy L

AU - Magnusson, Patrik K. E

AU - Spector, Tim D

AU - Widen, Elisabeth

AU - Silventoinen, Karri

AU - Kaprio, Jaakko

AU - Palotie, Aarno

AU - Peltonen, Leena

AU - GenomEUtwin Project

PY - 2007

Y1 - 2007

N2 - 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 tencentimorgan 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).

AB - 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 tencentimorgan 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).

KW - 314 Health sciences

U2 - 10.1371/journal.pgen.0030097

DO - 10.1371/journal.pgen.0030097

M3 - Article

VL - 3

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 6

ER -