Genotype-by-sex interaction in the aetiology of type 2 diabetes mellitus

Support for sex-specific quantitative trait loci in Hypertension Genetic Epidemiology Network participants

C. L. Avery, B. I. Freedman, A. T. Kraja, I. B. Borecki, M. B. Miller, J. S. Pankow, D. Arnett, C. E. Lewis, R. H. Myers, Steven Hunt, K. E. North

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aims/hypothesis: While there are sex-related differences in both the prevalence of type 2 diabetes mellitus and disease risk factors, there is only limited research on sex-specific influences on type 2 diabetes aetiology within the same study population. Thus, we assessed genotype-by-sex interaction using a liability threshold model in an attempt to localise sex-specific type 2 diabetes quantitative trait loci (QTLs). Subjects, materials and methods: Hypertensive siblings and their offspring and/or parents in the Hypertension Genetic Epidemiology Network of the Family Blood Pressure Program were recruited from five field centres. The diabetic phenotype was adjusted for race, study centre, age and non-linear age effects. In total, 567 diabetic individuals were identified in 385 families. Variance component linkage analyses in the combined sample and stratified by sex and race were performed (SOLAR program) using race-specific marker allele frequencies derived from a random sample of participants at each centre. Results: We observed a QTL-specific genotype-by-sex interaction (p=0.009) on chromosome 17 at 31 cM, with females displaying a robust adjusted logarithm of odds (LOD) of 3.0 compared with 0.2 in males and 1.3 in the combined sample. Three additional regions demonstrating suggestive evidence for linkage were detected: chromosomes 2 and 5 in the female sample and chromosome 22 (adjusted LOD=1.9) in the combined sample. Conclusions/ interpretation: These findings suggest that multiple genes may regulate susceptibility to type 2 diabetes, demonstrating the importance of considering the interaction of genes and environment in the aetiology of common complex traits.

Original languageEnglish
Pages (from-to)2329-2336
Number of pages8
JournalDiabetologia
Volume49
Issue number10
DOIs
Publication statusPublished - Oct 2006
Externally publishedYes

Fingerprint

Molecular Epidemiology
Quantitative Trait Loci
Type 2 Diabetes Mellitus
Genotype
Hypertension
Chromosomes, Human, Pair 22
Gene-Environment Interaction
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 2
Gene Frequency
Sex Characteristics
Siblings
Parents
Blood Pressure
Phenotype
Research
Population
Genes

Keywords

  • Genome scan
  • Genotype-by-sex interaction
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Genotype-by-sex interaction in the aetiology of type 2 diabetes mellitus : Support for sex-specific quantitative trait loci in Hypertension Genetic Epidemiology Network participants. / Avery, C. L.; Freedman, B. I.; Kraja, A. T.; Borecki, I. B.; Miller, M. B.; Pankow, J. S.; Arnett, D.; Lewis, C. E.; Myers, R. H.; Hunt, Steven; North, K. E.

In: Diabetologia, Vol. 49, No. 10, 10.2006, p. 2329-2336.

Research output: Contribution to journalArticle

Avery, C. L. ; Freedman, B. I. ; Kraja, A. T. ; Borecki, I. B. ; Miller, M. B. ; Pankow, J. S. ; Arnett, D. ; Lewis, C. E. ; Myers, R. H. ; Hunt, Steven ; North, K. E. / Genotype-by-sex interaction in the aetiology of type 2 diabetes mellitus : Support for sex-specific quantitative trait loci in Hypertension Genetic Epidemiology Network participants. In: Diabetologia. 2006 ; Vol. 49, No. 10. pp. 2329-2336.
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AU - Myers, R. H.

AU - Hunt, Steven

AU - North, K. E.

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