title: A locus on chromosome 1p36 is associated with thyrotropin and thyroid function as identified by genome-wide association study.
abstract: Thyroid hormones are key regulators of cellular growth, development, and metabolism, and thyroid disorders are a common cause of ill health in the community. Circulating concentrations of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) have a strong heritable component and are thought to be under polygenic control, but the genes responsible are mostly unknown. In order to identify genetic loci associated with these metabolic phenotypes, we performed a genome-wide association study of 2,120,505 SNPs in 2014 female twins from the TwinsUK study and found a significant association between rs10917469 on chromosome 1p36.13 and serum TSH (p = 3.2 × 10(-8)). The association of rs10917469 with serum TSH was replicated (p = 2.0 × 10(-4)) in an independent community-based sample of 1154 participants in the Busselton Health Study. This SNP is located near CAPZB, which might be a regulator of TSH secretion and thus of pituitary-thyroid axis function. Twenty-nine percent of white individuals carry the variant, and the difference in mean TSH concentrations between wild-type individuals and those homozygous for the minor G allele was 0.5 mU/l, which is likely to be clinically relevant. We also provide evidence of suggestive association (p < 5.0 × 10(-6)) of other SNPs with serum TSH, free T4, and free T3 concentrations, and these SNPs might be good targets for further studies. These results advance understanding of the genetic basis of pituitary-thyroid axis function and metabolic regulation.
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
authors.forename: Vijay
authors.initials: V
authors.lastname: Panicker
authors.forename: Scott G
authors.initials: SG
authors.lastname: Wilson
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Brown
authors.forename: John P
authors.initials: JP
authors.lastname: Beilby
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Bremner
authors.forename: Gabriela L
authors.initials: GL
authors.lastname: Surdulescu
authors.forename: Emad
authors.initials: E
authors.lastname: Qweitin
authors.forename: Irina
authors.initials: I
authors.lastname: Gillham-Nasenya
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Ee M
authors.initials: EM
authors.lastname: Lim
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fletcher
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood / Q000235:genetics*; D055815:Young Adult
chemical_list: D013972:Thyrotropin
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