Genetic loci linked to pituitary-thyroid axis set points: a genome-wide scan of a large twin cohort

TY - JOUR

T1 - Genetic loci linked to pituitary-thyroid axis set points

T2 - a genome-wide scan of a large twin cohort

AU - Panicker, Vijay

AU - Wilson, Scott G

AU - Spector, Tim D

AU - Brown, Suzanne J

AU - Kato, Bernet S

AU - Reed, Peter W

AU - Falchi, Mario

AU - Richards, J Brent

AU - Surdulescu, Gabriela L

AU - Lim, Ee M

AU - Fletcher, Steven J

AU - Walsh, John P

PY - 2008/9

Y1 - 2008/9

N2 - 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.DESIGN: 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.

AB - 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.DESIGN: 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.

KW - Adult

KW - Chromosome Mapping

KW - Chromosomes, Human

KW - Cohort Studies

KW - Female

KW - Genetic Linkage

KW - Genome, Human

KW - Humans

KW - Lod Score

KW - Middle Aged

KW - Pituitary Gland

KW - Quantitative Trait Loci

KW - Thyroid Gland

KW - Thyrotropin

KW - Thyroxine

KW - Triiodothyronine

KW - Twins, Dizygotic

U2 - 10.1210/jc.2007-2650

DO - 10.1210/jc.2007-2650

M3 - Article

C2 - 18611976

SN - 1945-7197

VL - 93

SP - 3519

EP - 3523

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 9

ER -