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

M. Perola, S. Sammalisto, T. Hiekkalinna, N.G. Martin, P.M. Visscher, GW Montgomery, B. Benyamin, J.R. Harris, D.I. Boomsma, G. Willemsen, J.J. Hottenga, K. Christensen, K. Kyvik, T.I.A. Sorensen, N.L. Pedersen, P.K.E. Magnusson, T.D. Spector, E. Widen, K. Silventoinen, J Kaprio & 2 others A. Palotie, L. Peltonen

Research output: Contribution to JournalArticleAcademicpeer-review

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). © 2007 Perola et al.
Original languageEnglish
Article numbere97
Number of pages10
JournalPLoS Genetics
Volume3
Issue number6
DOIs
Publication statusPublished - 2007

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Quantitative Trait Loci
Software
genome
Genome
Chromosomes, Human, Pair 20
loci
Chromosomes, Human, Pair 7
Body Height
Denmark
Finland
Sweden
Netherlands
Microsatellite Repeats
software
etiology
heritability
quantitative trait loci
chromosome
Population
Genes

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Perola, M., Sammalisto, S., Hiekkalinna, T., Martin, N. G., Visscher, P. M., Montgomery, GW., ... Peltonen, L. (2007). Combined genome scans for body stature in 6,602 European twins: Evidence for common Caucasian loci. PLoS Genetics, 3(6), [e97]. https://doi.org/10.1371/journal.pgen.0030097
Perola, M. ; Sammalisto, S. ; Hiekkalinna, T. ; Martin, N.G. ; Visscher, P.M. ; Montgomery, GW ; Benyamin, B. ; Harris, J.R. ; Boomsma, D.I. ; Willemsen, G. ; Hottenga, J.J. ; Christensen, K. ; Kyvik, K. ; Sorensen, T.I.A. ; Pedersen, N.L. ; Magnusson, P.K.E. ; Spector, T.D. ; Widen, E. ; Silventoinen, K. ; Kaprio, J ; Palotie, A. ; Peltonen, L. / Combined genome scans for body stature in 6,602 European twins: Evidence for common Caucasian loci. In: PLoS Genetics. 2007 ; Vol. 3, No. 6.
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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). {\circledC} 2007 Perola et al.",
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Perola, M, Sammalisto, S, Hiekkalinna, T, Martin, NG, Visscher, PM, Montgomery, GW, Benyamin, B, Harris, JR, Boomsma, DI, Willemsen, G, Hottenga, JJ, Christensen, K, Kyvik, K, Sorensen, TIA, Pedersen, NL, Magnusson, PKE, Spector, TD, Widen, E, Silventoinen, K, Kaprio, J, Palotie, A & Peltonen, L 2007, 'Combined genome scans for body stature in 6,602 European twins: Evidence for common Caucasian loci.' PLoS Genetics, vol. 3, no. 6, e97. 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, M.; Sammalisto, S.; Hiekkalinna, T.; Martin, N.G.; Visscher, P.M.; Montgomery, GW; Benyamin, B.; Harris, J.R.; Boomsma, D.I.; Willemsen, G.; Hottenga, J.J.; Christensen, K.; Kyvik, K.; Sorensen, T.I.A.; Pedersen, N.L.; Magnusson, P.K.E.; Spector, T.D.; Widen, E.; Silventoinen, K.; Kaprio, J; Palotie, A.; Peltonen, L.

In: PLoS Genetics, Vol. 3, No. 6, e97, 2007.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Combined genome scans for body stature in 6,602 European twins: Evidence for common Caucasian loci.

AU - Perola, M.

AU - Sammalisto, S.

AU - Hiekkalinna, T.

AU - Martin, N.G.

AU - Visscher, P.M.

AU - Montgomery, GW

AU - Benyamin, B.

AU - Harris, J.R.

AU - Boomsma, D.I.

AU - Willemsen, G.

AU - Hottenga, J.J.

AU - Christensen, K.

AU - Kyvik, K.

AU - Sorensen, T.I.A.

AU - Pedersen, N.L.

AU - Magnusson, P.K.E.

AU - Spector, T.D.

AU - Widen, E.

AU - Silventoinen, K.

AU - Kaprio, J

AU - Palotie, A.

AU - Peltonen, L.

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). © 2007 Perola et al.

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). © 2007 Perola et al.

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

M1 - e97

ER -