Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci.
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).
Perola
Markus
M
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
Sammalisto
Sampo
S
Hiekkalinna
Tero
T
Martin
Nick G
NG
Visscher
Peter M
PM
Montgomery
Grant W
GW
Benyamin
Beben
B
Harris
Jennifer R
JR
Boomsma
Dorret
D
Willemsen
Gonneke
G
Hottenga
Jouke-Jan
JJ
Christensen
Kaare
K
Kyvik
Kirsten Ohm
KO
Sørensen
Thorkild I A
TI
Pedersen
Nancy L
NL
Magnusson
Patrik K E
PK
Spector
Tim D
TD
Widen
Elisabeth
E
Silventoinen
Karri
K
Kaprio
Jaakko
J
Palotie
Aarno
A
Peltonen
Leena
L
D000328:Adult; D001827:Body Height / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D014429:Twins, Dizygotic / Q000208:ethnology* / Q000235:genetics*; D044465:White People