Volume 27 PANEL DISCUSSION ON HYPERTHYROIDISM TABLE 1. Examination on 207 propositi with Graves’ disease (28) No. examined : ’ Graves’ Simple Myxe- Total Mothers Sisters Aunts disease goiter dema 6 17 10 23 1 14 Daughters 18 20 Fathers Brothers Uncles 3 1 Sons 1 8 > Soir 201 363 188 213 137 22 667 2 554 377 659 26.1%. Martin and Fisher (28) studied the families of 90 propositi with Graves’ disease. As shown in Table 2, a total of 20 cases of thyrotoxicosis and 16 of simple goiter was found. The effect was more marked in Graves’ disease families than in goiter families. Again the condition was seen more in.female relatives than in male relatives. Finally, Boas and Ober (29) found that 11 of 143 blood relatives in ” five generations had exophthalmic goiter. Of this group, eight were females and three were males. From these data, it would appear that hyperthyroidism certainly was more prominent in these families, but TABLE 2. Observations in 90 families with Graves’ disease (28) Graves’ Toxic Simple Goiter disease goiter goiter (? toxic) Aunts 8 & 1 5013) 1 5 2 3 . 3 1 4 pie Graves’ Simple All disease goiter goiters 191 248 3.5 8.2 5.2 9.7 8.7 17.9 47 9.0 17.1 26.1 581 0 2.7 Fe 3.3 % 5.9 227 547 51 propositi showed toxic diffuse goiter. Making the necessary allowance for the inequality in sex and age distribution and estimating the risk of Graves’ disease or toxic diffuse goiter by examining a control population, it was possible to assess the frequency of the gene for thyroid disease at about 12.6%. As shown in Table 1, the risk of developing goiter is greater in females, with the risk in daughters rising to Mothers Fathers Sisters Brothers Sons Daughters . Graves Risk of development Total 6 0 16 8 0 1 5 did not follow an autosomal dominant autosomal recessive, or sex-linked mode of inheritance. It may be worthwhile to speculate on the possibility that hyperthyroidism may be transmitted on the basis of a multifactorial inheritance. Most differences between normal human beings show continuous variance. For example, if 1000 men @ were arranged in order of height, each would differ from his neighbor by an exceedingly small amount. Yet this variation is influenced by heredity. Continuous variation cannot be explained on the basis of single genes, but must depend on the combined action of a number of genes, or of many genes. The regressions of child on parent, or parent on child, or sib on sib, are equal to the numberof genes in common, and this is also true for more remote relationships, as shown in Table 3. Holt (30) examined the fingerprint ridge-count resemblances between relatives (Table 4) and found a goodcorrelation with the theoretical number of genes in common. It is conceivable that hyperthyroidism represents a type of polygenic inheritance except that the condition is seen with greater frequency among females, possibly because of a hormonal effect. DR. WERNER:If LATS is accepted asan etiologic agent, and if it is accepted that 3 it might be an antibody, what would be “gill found in the serum ofrelatives that did not