Genetic loci linked to pituitary-thyroid axis set points: a genome-wide scan of a large twin cohort.
OBJECTIVE
Previous studies have shown that circulating concentrations of TSH, free T4, and free T3 are genetically regulated, but the genes responsible remain largely unknown. The aim of this study was to identify genetic loci associated with these parameters.


METHODS
We performed a multipoint, nonparametric genome-wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history of thyroid disease. The genome scan comprised 737 microsatellite markers supplemented with dinucleotide markers. Data were analyzed using residualized thyroid hormone data after adjustment for age, smoking, and body mass index.


RESULTS
Multipoint linkage analysis gave linkage peaks for free T4 on chromosome 14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32, and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0-2.3).


CONCLUSIONS
This study has identified eight genomic locations with linkage of LOD of 2.0 or greater. These results should enable targeted positional candidate and positional cloning studies to advance our understanding of genetic control of the pituitary-thyroid axis.
Panicker
Vijay
V
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia 6009.
Wilson
Scott G
SG
Spector
Tim D
TD
Brown
Suzanne J
SJ
Kato
Bernet S
BS
Reed
Peter W
PW
Falchi
Mario
M
Richards
J Brent
JB
Surdulescu
Gabriela L
GL
Lim
Ee M
EM
Fletcher
Steven J
SJ
Walsh
John P
JP
D000328:Adult; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D010902:Pituitary Gland / Q000502:physiology*; D040641:Quantitative Trait Loci; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood / Q000235:genetics; D013974:Thyroxine / Q000097:blood / Q000235:genetics; D014284:Triiodothyronine / Q000097:blood / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics* / Q000502:physiology
D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine