Diabetologia

, Volume 37, Issue 12, pp 1231–1240 | Cite as

Segregation analysis of NIDDM in Caucasian families

  • J. T. E. Cook
  • D. C. Shields
  • R. C. L. Page
  • J. C. Levy
  • A. T. Hattersley
  • J. A. G. Shaw
  • H. A. W. Neil
  • J. S. Wainscoat
  • R. C. Turner
Originals

Summary

Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypotheses, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.

Key words

Non-insulin-dependent diabetes mellitus genetic epidemiology genetic linkage 

Abbreviations

MODY

Maturity onset diabetes of the young

IDDM

insulin-dependent diabetes mellitus

NIDDM

non-insulin-dependent diabetes mellitus

FPG

fasting plasma glucose

AIC

Akaike Information criterion

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • J. T. E. Cook
    • 1
  • D. C. Shields
    • 2
  • R. C. L. Page
    • 1
  • J. C. Levy
    • 1
  • A. T. Hattersley
    • 1
  • J. A. G. Shaw
    • 1
  • H. A. W. Neil
    • 3
  • J. S. Wainscoat
    • 4
  • R. C. Turner
    • 1
  1. 1.Diabetes Research LaboratoriesClinical Reader, Radcliffe InfirmaryOxfordUK
  2. 2.CRC Genetic Epidemiology Research Group, Department of Child HealthUniversity of SouthamptonUK
  3. 3.Department of Public Health and Primary CareUniversity of OxfordUK
  4. 4.Department of HaematologyJohn Radcliffe HospitalOxfordUK

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