Risk of diabetes in siblings of index cases with Type 2 diabetes: implications for genetic studies.
OBJECTIVE
The goal was to estimate the sibling recurrence-risk ratio for Type 2 diabetes in families with diabetes occurring in middle age. Because diabetes aetiology involves environmental exposures and genetic susceptibility, we sought to identify determinants of the recurrence risk.


METHODS
We surveyed patients diagnosed at ages 35-59 years (n = 563) to obtain information on the occurrence of diabetes in their relatives, particularly siblings (n = 1675). Age-specific prevalences of diabetes in the US population were used for comparison.


RESULTS
The overall sibling recurrence-risk ratio for diabetes was low, about 1.8 in the Joslin families and even lower in three other studies that were reanalysed for comparison. In all studies, the diabetes risk in siblings of index cases without a history of diabetes in a parent was similar to that in the general population, suggesting that genetic factors contributed to the occurrence of diabetes in only a minority of these siblings. The fact that recurrence-risk ratios were elevated only in families with one or two diabetic parents indicates that susceptibility to Type 2 diabetes is transmitted primarily through an affected parent. In addition, the sibling recurrence-risk ratios were elevated even further in families with diabetes in both a parent and grandparent of the index case, and in siblings of non-obese index cases (percent ideal body weight < 120%).


CONCLUSIONS
The selection of families with non-obese index cases and vertical transmission of diabetes through three generations may improve the success of efforts to map susceptibility genes for Type 2 diabetes.
Weijnen
C F
CF
Research Division, Joslin Diabetes Center, Wake Forest University School of Medicine, Winston Salem, NC, USA.
Rich
S S
SS
Meigs
J B
JB
Krolewski
A S
AS
Warram
J H
JH
D000328:Adult; D017668:Age of Onset; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009679:Nuclear Family; D009765:Obesity; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology