COMPLEX GENETICS
COMPARATIVE GENOMICS CENTRE

Mail Address: Comparative Genomics Centre,
Molecular Sciences Bldg 21, James Cook University,
Townsville, 4811, Queensland, Australia
Telephone: 61-7-4781 6265 Fax:  61-7-4781 6078

AN EXERCISE IN CALCULATING DISEASE SUSCEPTIBILITY

Materials:

A copy of Onkamo et al, Diabetologia (1999) 42: 1395-1403
[Click to download]
A copy of Baxter, Autoimmunity (1997) 25: 177-189
[Click to download]
A copy of Appendix A of Falconer, Ann Hum Genet Lond (1965) 29:72-74
[Click to download]
GeneRiskCalc Microsoft Excel spreadsheet
[Click to download]
A copy of a primary research manuscript containing concordance data for relatives of patients with diabetes.
To be provided in session
Instructions:
1.        Find a concordance figure for type 1 diabetes in relatives of patients with diabetes in the primary research manuscript. Note the relationship of the relatives to the patients, the country and approximate year of study.

2.        Identify the incidence of type 1 diabetes in the general community of that country, estimating the incidence for that year from the figures published in Onkamo et al.

3.        Convert the incidence figure from Onkamo et al from per 100,000 to percent by dividing by 1,000, and from per year to life time risk by multiplying by 30.

4.        Use the GeneRiskCalc Excel spreadsheet to calculate the heritability for type 1 diabetes in the country and year for the primary research manuscript provided.

5.        Repeat the calculation using Falconer's tables. Brief instructions are provided below. The Baxter manuscript contains a more detailed description of the procedure.

6.        Is there a difference in the heritability calculated using the two methods? Why?

7.        Use the figure for heritability obtained from the GeneRiskCalc Excel spreadsheet, and the population incidence obtained above to calculate the risk of developing type 1 diabetes for the following:
        a) Child of a patient with type 1 diabetes
        b) Sibling of a patient with type 1 diabetes
        c) Child of a patient with schizophrenia
        d) Grandchild of a patient with type 1 diabetes
        e) Child of a patient with type 2 diabetes
        f) Identical twin of a patient with type 1 diabetes
        8. Bring all results to the synthesis session.

Calculating Heritability using Falconer's Appendix:
Step 1: Determine the incidences of the trait in the general population, and in a select group of relatives of patients, for which the distance of the relationship is know, e.g. identical twins, siblings, grand children etc.
Step 2: Express each incidence of the trait in terms of the threshold distance from the mean, x (in standard deviations), from the table in Appendix A of Falconer.
Step 3: Where
xg is x for the general population
and
xr is x for the relatives,
Calculate the difference, 
xg-xr
Step 4: Determine a, the mean deviation of liability of affected individuals in the general population from the mean liability of the general population, (in standard deviations) from the table in Appendix A of Falconer
Step 5: Calculate the Regression Coefficient, b
b = (xg-xr)/a
Step 6: Calculate heritability, h2
     h2 = b/r

Where
If the relatives are identical twins, r=1
If the relatives are siblings/progeny, r=0.5
If the relatives are 2nd degree, r=0.25
etc.


OTHER GENETICS LINKS: OTHER LINKS: Comparative Genomics Centre, James Cook University, Key words: Autoimmune diabetes, Type 1 diabetes mellitus, childhood diabetes, lupus, systemic lupus erythematosus, haemolytic anaemia, hemolytic anemia, Coombs' test, antinuclear antibodies, renal failure, glomerulonephritis, gastritis, type A gastritis, pernicious anemia.