Am JHum Genet 29:76-82, 1977
A Genetic and Epidemiologic Study of Periodontal Disease in Hawali. II. Genetic and Environmental Influence C. S. CHUNG,1 M. C. W. KAU,2 S. S. C. CHUNG,' AND D. C. RAO3
Periodontal disease is characterized by inflammation and/or destruction of supporting tissues of the tooth. About one-fourth of the adult population of the United States suffers from destructive periodontal disease [1]. A number of epidemiologic factors such as age, sex, oral hygiene, and socioeconomic status, associated with the risk of this disease, were discussed in a recent review [2]. The adverse effects of cigarette smoking on periodontal health is less firmly established [3-7]. However, these factors separately or in combination appear to explain a relatively small proportion of phenotypic variation of the disease [8]. Schull and Neel [9] showed a significant depressing effect of inbreeding on gingivitis among Japanese children, implicating possible involvement of major recessive genes. Consistent with this finding was the observation of Chung et al. [8] that major racial hybridity was associated with a higher level of periodontal health among schoolchildren in Hawaii. In an attempt to establish a genetic basis, some investigators studied the possible association of known genetic markers with the risk of periodontal disease; the results are conflicting. Weber and Pastern [10] and Polevitzky [11 ] claimed an excess of blood type A among patients, whereas Pradhan et al. [12] showed a higher frequency of type 0. Barros and Witkop [13] found no association with the ABO blood groups. No association was found between secretor status and periodontal disease [12]. Only family studies can provide the critical information for establishing the mode of inheritance; however, data are scarce. Gorlin et al. [14] quotes A. Dickmann's conclusion that periodontal disease follows the dominant mode of inheritance [15], and twin studies [16, 17] suggest some degree of genetic involvement. The present study aims specifically to determine the relative influence of genetic and environmental factors on periodontal disease based on family data using path analysis. This is a sequel to the earlier work on the epidemiology of periodontal disease [7]. The previous study indicated a dichotomous distribution of periodontal disease scores among Received June 15, 1976; revised August 2, 1976. This study was supported in part by grants from the U. S. Public Health Service (DE 02646 and GM 17173). 1 Department of Public Health Sciences and Pacific Biomedical Research Center, University of Hawaii, Honolulu, Hawaii 96822. 2 Division of Dental Health, Hawaii State Department of Health, Honolulu, Hawaii 96813. 3Population Genetics Laboratory, University of Hawaii, Honolulu, Hawaii 96822. © 1977 by the American Society of Human Genetics. All rights reserved.
76
PERIODONTAL DISEASE IN HAWAII
77
racial groups studied; the group which included Caucasians, Japanese, and "others" was at a higher level of periodontal health than that which included Hawaiians, Filipinos, and Samoans [7]. The study also showed that inbreeding of the subject was not associated with the risk of periodontal disease, whereas cigarette smoking was found to have adverse effects on periodontal health. SUBJECTS AND DENTAL EXAMINATION
This study deals with only common periodontal disease and excludes such entities as PapillonLefevre syndrome [18] and periodontosis [19] which are considered etiologically distinct. Subjects and method of dental examination were detailed in the first paper [7 ]. The subjects were composed of volunteer families in which both natural parents with at least one child age 14 or above were available for dental examination. A few exceptions were made when younger children wished to be included in the study with the rest of the family. Diverse racial groups were represented in the sample though relatively large numbers were Caucasians, Japanese, Filipinos, Hawaiians or part-Hawaiians, and Samoans [7]. Periodontal condition was scored by the method of Ramfjord [20] with minor modification. The technique included examinations of gingivitis, depth of periodontal pocket, calculus, contact, attrition, mobility, and plaque. The modification was in the method of judging the depth of periodontal pocket. Instead of converting to scores, we used actual measurements in millimeters of the distance between the cementum-enamel junction and the bottom of the periodontal pocket when the crevice extended apically relative to the junction. A score of 0 was assigned when the pocket depth did not extend to the level of the cementum-enamel junction. Pocket depths were measured on four surfaces (buccal, lingual, mesial, and distal) of the six teeth specified by Ramfjord. The average pocket depth of an individual was obtained by averaging the mean pocket depths of the examined teeth. METHOD OF ANALYSIS
The general periodontal health of a subject was measured by an index derived from the first principal component equation. The previous analysis showed the strength of principal component analysis applied to these data, and the first principal component accounted for 46% of the total variance [7]. The associated eigenvector derived from the correlation matrix is given in table 1. Principal component scores were further adjusted for age, age TABLE 1 EIGENVECTOR ASSOCIATED WITH FIRST PRINCIPAL COMPONENT Gingivitis
Average Pocket
Deepest Pocket
Calculus
Contact
Attrition
Mobility
Plaque
Eigenvalue
0.378
0.468
0.468
0.394
0.166
0.307
0.336
0.169
3.67
squared, sex, and smoking history by the regression method since these variables were shown to be significantly associated with the component [7]. For genetic analysis of the family data, path analysis was employed. The method was originally developed by Wright [21 ] and extended recently by Morton [22] and Rao et al. [23] to human genetics. The extended method used here evaluates common environment and tests the hypothesis on different paths [23]. The analysis of our data* involved two * The computer program SUPERVAR on the CDC 3100 of the Population Genetics Laboratory of the University of Hawaii was used for analysis of the present data.
78
CHUNG ET AL.
models, using correlations for full sibs for one and parent-offspring for the other. Correlation between full sibs is decomposed into C2 + g2, where c is the path from common family environment to the phenotype of the child and g is the path from the midparent genotype to the phenotype of the child, assuming no correlation between the midparent genotype and common home environment [23]. These relationships are depicted in figure 1. The path g is related to heritability (h2) by g = h/\/2under the assumption of no assortative mating. Environment common to members of the same family is measured by the family index (I). Parent-offspring correlation is expressed as c2k + g2z, where k and z are such that ck is the path coefficient from the common environment to the phenotype of a parent, andhz is the path coefficient from the genotype to the phenotype of the parent (fig. 2). Family index was derived from the prediction equation obtained by regressing principal component scores on the occupation of the father, mean number of years of education of the parents, and race of the child. Thus the equation used was: Y = A + bjx1 + b2x2 + b3x3 + b4x4 + b5x5 + bx6 + b7x7 + b8x8 + b9x9, where A = constant; b = partial regression coefficient;x1 = father's occupation (1 = high, 2 = intermediate, 3 = low, see reference [24]); x2 = x 1 squared; X3 = mean number of years of education of both parents;x4 =x3squared;x5 = Japanese (1 = Japanese, 0 = otherwise);x6 = Filipino (1 = Filipino, 0 = otherwise); X7 = Hawaiian or part-Hawaiian (1 = Hawaiian or part-Hawaiian, 0 = otherwise);x8 = Samoan (1 = Samoan, 0= otherwise);x9 = other (1 = other, 0 = otherwise). The basis of the racial classification appears in the first paper [7]. Race was included in the family index because the observed racial variation in the prevalence of periodontal disease appeared to be predominantly of environmental origin [7].
[g~~
g
FIG. 1 Path diagram forfull sib correlation. Oi = phenotype of the ith child; G, = mid-parentgenotype;C = common family environment; and I = index for common family environment.
PERIODONTAL DISEASE IN HAWAII
79
i
ek
c
hz
g
FIG. 2 -Path diagram for parent and offspring correlation. Gr and P = genotype and phenotype of a parent, respectively; Gp = mid-parent genotype; 0 = phenotype of a child; C = common family environment; andl = index for common family environment.
RESULTS
Table 2 shows the familial correlations between phenotypes and between family index and phenotype wheren is related to the number of pairs associated with the correlation. The actual numbers of pairs used for the computation were larger than those given. It should be noted that the correlation between parent and family index is markedly high (.603) in contrast to the parent-offspring correlation (. 384). It is also noteworthy that the correlation between sibs (.494) and between sib and family index (.487) are of similar magnitude. The observations show that undoubtedly environmental factors play a major role in the variation of periodontal disease, especially in the parental generation. Thus, we tested the hypothesis that the heritability in the parental generation is nil (z = 0), and the effect of common environment is the same for both parent and offspring generations (k = 1), estimating from the data h (square root of heritability in the offspring generation), c (path coefficient from common environment to the phenotype in the offspring generation), and i (path coefficient from common environment to the index). The TABLE 2 CORRELATIONS BETWEEN PHENOTYPES
AND BETWEEN
Source
Between sibs .......................... Sib and index .......................... Parent and offspring ..................... Parent and index .......................
PHENOTYPE AND FAMILY INDEX
Correlation
n
Type of Correlation
.494
82 249 235 241
Intraclass Interclass Interclass Interclass
.487 .384 .603
CHUNG ET AL.
80
TABLE 3 TESTS OF HYPOTHESES ON DIFFERENT PARAMETERS Hypothesis
X2
df
k =1,z =0 ............... 1 k =1,z =0, h =0 ......... 2 k = 1,z =0, c =i =0 ....... 3
3.31 4.38 222.74
.466 + .219 0 .992 ± .082
Cc
k
z
.619 ± .045 .642 ± .037 0
1 1 1
0 0 0
.882 ± .082 .850 ± .070 0
result given in table 3 shows that the fit is indeed good (X2i = 3.31 ,P = .07). Therefore, we will treat this as the basic model. We can now proceed with tests of null hypotheses on h, c, and i (table 3). The hypothesis of h = 0 cannot be rejected (X2i = 4.38 -3.31 = 1.07,P = .30). On the other hand, the hypothesis of c = i = 0 has a remarkably poor fit to the data (X22 = 222.74 - 3.31 = 219.43, P 0). Table 4 shows the breakdown of variance of periodontal disease score derived from the path analysis of the offspring generation. It should be noted that the heritability estimate (.217) has too large a standard error (.204) to be of significance. It is concluded from the data that heritability of periodontal disease is negligible, and common family environment is a major determinant of the variation of the condition. -
DISCUSSION
Analysis of our data failed to show the presence of an additive genetic component in the individual variation of the common form of periodontal disease. Theoretically, the failure to reject the null hypothesis of zero heritability could be attributed to the tendency that the sample sizes were consistently underestimated according to the method used here [23], leading to larger type II error. In any event, we can explore the possible magnitude of heritability under another model. Since the estimate of i is very large (.882 + .082), we can set i = 1 and fit the remaining four parameters h, c, k, and z, realizing that the model overestimates h since a larger value for i would lower c (hence elevate h). This leaves no more degrees of freedom to test the goodness of fit of the model, but the variance components can be estimated under the general model. The heritability estimates from this model were .511 + .195 and .064 + .092 for the offspring and parental generations, respectively. The estimate for offspring appears large, but its large standard error vitiates the overestimated value of heritability. Interestingly, the result also supports the proposition that the TABLE 4 COMPONENTS OF VARIANCE ESTIMATED FROM FULL SIB DATA UNDER THE MODEL OF K = 1 AND Z = 0 Proportion of Variance
Component
Genotype (h2) ..217 Common environment (c2) Residual
..383
..400
Total .1.000
Standard Error
.204 .056 .180 ...
PERIODONTAL DISEASE IN HAWAII
81
parental generation has lower heritability than the offspring generation, which is consistent with the finding in human intelligence [23]. Under this model the variance components for common family environment were estimated to be .236 + .047 and .363 + .050 for children and parents, respectively, showing considerable degree of stability. A genetic study on periodontal disease involving intergenerational family members is complicated by association of age with the risk of the disease. An investigator is therefore limited to either studying multiple generation families with only older adults or studying families with little or no age restriction but with statistical adjustment for age differences. The present study took the latter alternative because of the obvious difficulty associated with the first choice under modern social conditions. The adjustment process used both age and age squared terms to remove the age effect as much as possible. Possible effects of age on variances for the two generations cannot be specified precisely. Path analysis with other conditions has demonstrated marked robustness of the method under the condition of considerable departure from homoscedasticity. The finding of insignificant genetic component from this study is in apparent conflict with the earlier observations of the depressing effect of inbreeding [9] and the favorable effect of racial hybridity [8]. However, it must be pointed out that these studies were done on children and hence were largely concerned with gingivitis, which is a mild and reversible symptom of periodontal disease. Our previous study [7] suggested that gingivitis may be characterized in two ways: (1) the condition occurs in association with other destructive signs of the disease as represented by the first principal component, the subject of the present study; and (2) gingivitis is simply an isolated symptom in response to action of bacterial plaque on the tooth as characterized by the second principal component [7]. It is likely that gingivitis, on which the effects of inbreeding and racial hybridity were demonstrated, belonged to the latter class or was of mixed origin. An alternative explanation for the observed inconsistency between this study and the earlier work is that environmental effects associated with inbreeding or hybridity were incompletely removed from the covariance analysis in the earlier studies. The significance of family environment in the etiology of periodontal disease has been clearly demonstrated in the present study. SUMMARY
In order to determine the relative influence of genetic and environmental factors in periodontal disease, path analysis has been applied to 241 nuclear families. Common family environment was represented by an index. The data failed to detect significant heritability, and common family environment proved to be a major determinant in the variation of periodontal health. ACKNOWLEDGMENTS The authors are greatly indebted to the co-investigators of the Behavioral Biology Laboratory of the University of Hawaii, who saw that the subjects of their study on cognitive ability were made available to this study. Professor Yoshi Koga of the Department of Dental Hygiene kindly made their dental facility available to this project. The authors are also grateful to Mrs. Linda Kumasaka and Mrs. Carol Hiraoka, who provided invaluable technical assistance for this study. The assistance of Dr. S. A. Schendel at the initial phase of this study is also appreciated. Mr. Richard Johnson kindly made arrangements to examine some subjects at the Schofield Barracks.
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CHUNG ET AL.
REFERENCES 1. KELLY JE, VAN KIRK E: Periodontal disease in adults: United States 1960-1962. National Center for Health Statistics, series 11, no. 12, 1965 2. MCMILLAN RS, WOLFF AE: Periodontal disease, in The Epidemiology of Oral Health, edited by PELTON WJ, DUNBAR JB, MCMILLAN RS, MOLLER P. WOLFF AE, Cambridge, Mass., Harvard Univ. Press, 1969 3. ARNO A, SCHEI 0, LOVDAL A, WAEHAUG F: Alveolar bone loss as a function of tobacco consumption. Acta Odontol Scand 17:3-10, 1959 4. LILIENTHAL B, AMERENA V, GREGORY V: An epidemiological study of chronic periodontal disease. Arch Oral Biol 10:553-566, 1965 5. SUMMERS CJ, OBERMAN A: Association of oral disease with 12 selected variables: I. Periodontal disease. J Dent Res 47:457-462, 1968 6. PREBER H, KANT T: Effect of tobacco-smoking on periodontal tissue of 15-year-old schoolchildren. J Periodont Res 8:278-283, 1973 7. CHUNG CS, KAU MCW, CHUNG SSC, SCHENDEL SA: A genetic and epidemiologic study of periodontal disease in Hawaii: I. Racial and other epidemiologic factors. J Periodont Res. In press, 1976 8. CHUNG CS, RUNCK DW, NISWANDER JD, BILBEN SE, KAU MCW: Genetic and epidemiologic studies of oral characteristics in Hawaii's schoolchildren. I. Caries and periodontal disease. J Dent Res 49:1374- 1385, 1970 9. SCHULL WJ, NEEL JV: The Effects of Inbreeding on Japanese Children. New York, Harper & Row, 1965 10. WEBER R, PASTERN W: Uber die Frage der konstitutionellen Bereitschaft zur sog Alveolar-pyorrhoe. Dtsch Mschr Zahnerlk 45:704-709, 1927 11. POLEVITZKY K: Blood types in pyorrhea alveolaris. J Dent Res 9:285, 1929 12. PRADHAN AC, CHAWLA TN, SAMUEL KC, PRADHAN S: The relationship between periodontal disease and blood groups and secretor status. J Periodont Res 6:294-300, 1971 13. BARROS L, WITKOP CJ: Oral and genetic study of Chileans 1960. III. Periodontal disease and
nutritional factors. Arch Oral Biol 8:195-206, 1963 14. GORLIN RJ, STALLARD RE, SHAPIRO BL: Genetics and periodontal disease. J Periodontol 38:5-10, 1967 15. DICKMANN A: Die Vererbung der Paradentose. Ph.D. Diss., Munchen, 1935 16. REISER HF, VOGEL F: Uber die Erblichkeit der Zahnsteinbildung beim Menschen. Dtsch Zahnarztl Weschr 38:1355- 1358, 1958 17. CIANCIO SG, HAZEN SP, CUNAT JJ: Periodontal observations in twins. J Periodont Res 4:42-45, 1969 18. PERRIMAN AO: Papillon-Lefevre syndrome. Br Dent J 123:484-488, 1967 19. BENJAMIN SD, BAER PN: Familial patterns of advanced alveolar bone loss in adolescence (periodontosis). Periodontics 5:82-88, 1967 20. RAMFJORD SP: Indices for prevalence and incidence of periodontal disease. J Periodontol 30:51-59, 1959 21. WRIGHT S: Correlation and causation. J Agric Res 20:557-585, 1921 22. MORTON NE: Analysis of family resemblance. I. Introduction. Am J Hum Genet 26:318-330, 1974 23. RAO DC, MORTON NE, YEE S: Analysis of family resemblance. II. A linear model for family correlation. Am J Hum Genet 26:331- 359, 1974 24. MORTON NE, CHUNG CS, MI MP: Genetics of Interracial Crosses in Hawaii. Basel, S. Karger, 1967
A Genetic and Epidemiologic Study of Periodontal Disease in Hawali. II. Genetic and Environmental Influence C. S. CHUNG,1 M. C. W. KAU,2 S. S. C. CHUNG,' AND D. C. RAO3
Periodontal disease is characterized by inflammation and/or destruction of supporting tissues of the tooth. About one-fourth of the adult population of the United States suffers from destructive periodontal disease [1]. A number of epidemiologic factors such as age, sex, oral hygiene, and socioeconomic status, associated with the risk of this disease, were discussed in a recent review [2]. The adverse effects of cigarette smoking on periodontal health is less firmly established [3-7]. However, these factors separately or in combination appear to explain a relatively small proportion of phenotypic variation of the disease [8]. Schull and Neel [9] showed a significant depressing effect of inbreeding on gingivitis among Japanese children, implicating possible involvement of major recessive genes. Consistent with this finding was the observation of Chung et al. [8] that major racial hybridity was associated with a higher level of periodontal health among schoolchildren in Hawaii. In an attempt to establish a genetic basis, some investigators studied the possible association of known genetic markers with the risk of periodontal disease; the results are conflicting. Weber and Pastern [10] and Polevitzky [11 ] claimed an excess of blood type A among patients, whereas Pradhan et al. [12] showed a higher frequency of type 0. Barros and Witkop [13] found no association with the ABO blood groups. No association was found between secretor status and periodontal disease [12]. Only family studies can provide the critical information for establishing the mode of inheritance; however, data are scarce. Gorlin et al. [14] quotes A. Dickmann's conclusion that periodontal disease follows the dominant mode of inheritance [15], and twin studies [16, 17] suggest some degree of genetic involvement. The present study aims specifically to determine the relative influence of genetic and environmental factors on periodontal disease based on family data using path analysis. This is a sequel to the earlier work on the epidemiology of periodontal disease [7]. The previous study indicated a dichotomous distribution of periodontal disease scores among Received June 15, 1976; revised August 2, 1976. This study was supported in part by grants from the U. S. Public Health Service (DE 02646 and GM 17173). 1 Department of Public Health Sciences and Pacific Biomedical Research Center, University of Hawaii, Honolulu, Hawaii 96822. 2 Division of Dental Health, Hawaii State Department of Health, Honolulu, Hawaii 96813. 3Population Genetics Laboratory, University of Hawaii, Honolulu, Hawaii 96822. © 1977 by the American Society of Human Genetics. All rights reserved.
76
PERIODONTAL DISEASE IN HAWAII
77
racial groups studied; the group which included Caucasians, Japanese, and "others" was at a higher level of periodontal health than that which included Hawaiians, Filipinos, and Samoans [7]. The study also showed that inbreeding of the subject was not associated with the risk of periodontal disease, whereas cigarette smoking was found to have adverse effects on periodontal health. SUBJECTS AND DENTAL EXAMINATION
This study deals with only common periodontal disease and excludes such entities as PapillonLefevre syndrome [18] and periodontosis [19] which are considered etiologically distinct. Subjects and method of dental examination were detailed in the first paper [7 ]. The subjects were composed of volunteer families in which both natural parents with at least one child age 14 or above were available for dental examination. A few exceptions were made when younger children wished to be included in the study with the rest of the family. Diverse racial groups were represented in the sample though relatively large numbers were Caucasians, Japanese, Filipinos, Hawaiians or part-Hawaiians, and Samoans [7]. Periodontal condition was scored by the method of Ramfjord [20] with minor modification. The technique included examinations of gingivitis, depth of periodontal pocket, calculus, contact, attrition, mobility, and plaque. The modification was in the method of judging the depth of periodontal pocket. Instead of converting to scores, we used actual measurements in millimeters of the distance between the cementum-enamel junction and the bottom of the periodontal pocket when the crevice extended apically relative to the junction. A score of 0 was assigned when the pocket depth did not extend to the level of the cementum-enamel junction. Pocket depths were measured on four surfaces (buccal, lingual, mesial, and distal) of the six teeth specified by Ramfjord. The average pocket depth of an individual was obtained by averaging the mean pocket depths of the examined teeth. METHOD OF ANALYSIS
The general periodontal health of a subject was measured by an index derived from the first principal component equation. The previous analysis showed the strength of principal component analysis applied to these data, and the first principal component accounted for 46% of the total variance [7]. The associated eigenvector derived from the correlation matrix is given in table 1. Principal component scores were further adjusted for age, age TABLE 1 EIGENVECTOR ASSOCIATED WITH FIRST PRINCIPAL COMPONENT Gingivitis
Average Pocket
Deepest Pocket
Calculus
Contact
Attrition
Mobility
Plaque
Eigenvalue
0.378
0.468
0.468
0.394
0.166
0.307
0.336
0.169
3.67
squared, sex, and smoking history by the regression method since these variables were shown to be significantly associated with the component [7]. For genetic analysis of the family data, path analysis was employed. The method was originally developed by Wright [21 ] and extended recently by Morton [22] and Rao et al. [23] to human genetics. The extended method used here evaluates common environment and tests the hypothesis on different paths [23]. The analysis of our data* involved two * The computer program SUPERVAR on the CDC 3100 of the Population Genetics Laboratory of the University of Hawaii was used for analysis of the present data.
78
CHUNG ET AL.
models, using correlations for full sibs for one and parent-offspring for the other. Correlation between full sibs is decomposed into C2 + g2, where c is the path from common family environment to the phenotype of the child and g is the path from the midparent genotype to the phenotype of the child, assuming no correlation between the midparent genotype and common home environment [23]. These relationships are depicted in figure 1. The path g is related to heritability (h2) by g = h/\/2under the assumption of no assortative mating. Environment common to members of the same family is measured by the family index (I). Parent-offspring correlation is expressed as c2k + g2z, where k and z are such that ck is the path coefficient from the common environment to the phenotype of a parent, andhz is the path coefficient from the genotype to the phenotype of the parent (fig. 2). Family index was derived from the prediction equation obtained by regressing principal component scores on the occupation of the father, mean number of years of education of the parents, and race of the child. Thus the equation used was: Y = A + bjx1 + b2x2 + b3x3 + b4x4 + b5x5 + bx6 + b7x7 + b8x8 + b9x9, where A = constant; b = partial regression coefficient;x1 = father's occupation (1 = high, 2 = intermediate, 3 = low, see reference [24]); x2 = x 1 squared; X3 = mean number of years of education of both parents;x4 =x3squared;x5 = Japanese (1 = Japanese, 0 = otherwise);x6 = Filipino (1 = Filipino, 0 = otherwise); X7 = Hawaiian or part-Hawaiian (1 = Hawaiian or part-Hawaiian, 0 = otherwise);x8 = Samoan (1 = Samoan, 0= otherwise);x9 = other (1 = other, 0 = otherwise). The basis of the racial classification appears in the first paper [7]. Race was included in the family index because the observed racial variation in the prevalence of periodontal disease appeared to be predominantly of environmental origin [7].
[g~~
g
FIG. 1 Path diagram forfull sib correlation. Oi = phenotype of the ith child; G, = mid-parentgenotype;C = common family environment; and I = index for common family environment.
PERIODONTAL DISEASE IN HAWAII
79
i
ek
c
hz
g
FIG. 2 -Path diagram for parent and offspring correlation. Gr and P = genotype and phenotype of a parent, respectively; Gp = mid-parent genotype; 0 = phenotype of a child; C = common family environment; andl = index for common family environment.
RESULTS
Table 2 shows the familial correlations between phenotypes and between family index and phenotype wheren is related to the number of pairs associated with the correlation. The actual numbers of pairs used for the computation were larger than those given. It should be noted that the correlation between parent and family index is markedly high (.603) in contrast to the parent-offspring correlation (. 384). It is also noteworthy that the correlation between sibs (.494) and between sib and family index (.487) are of similar magnitude. The observations show that undoubtedly environmental factors play a major role in the variation of periodontal disease, especially in the parental generation. Thus, we tested the hypothesis that the heritability in the parental generation is nil (z = 0), and the effect of common environment is the same for both parent and offspring generations (k = 1), estimating from the data h (square root of heritability in the offspring generation), c (path coefficient from common environment to the phenotype in the offspring generation), and i (path coefficient from common environment to the index). The TABLE 2 CORRELATIONS BETWEEN PHENOTYPES
AND BETWEEN
Source
Between sibs .......................... Sib and index .......................... Parent and offspring ..................... Parent and index .......................
PHENOTYPE AND FAMILY INDEX
Correlation
n
Type of Correlation
.494
82 249 235 241
Intraclass Interclass Interclass Interclass
.487 .384 .603
CHUNG ET AL.
80
TABLE 3 TESTS OF HYPOTHESES ON DIFFERENT PARAMETERS Hypothesis
X2
df
k =1,z =0 ............... 1 k =1,z =0, h =0 ......... 2 k = 1,z =0, c =i =0 ....... 3
3.31 4.38 222.74
.466 + .219 0 .992 ± .082
Cc
k
z
.619 ± .045 .642 ± .037 0
1 1 1
0 0 0
.882 ± .082 .850 ± .070 0
result given in table 3 shows that the fit is indeed good (X2i = 3.31 ,P = .07). Therefore, we will treat this as the basic model. We can now proceed with tests of null hypotheses on h, c, and i (table 3). The hypothesis of h = 0 cannot be rejected (X2i = 4.38 -3.31 = 1.07,P = .30). On the other hand, the hypothesis of c = i = 0 has a remarkably poor fit to the data (X22 = 222.74 - 3.31 = 219.43, P 0). Table 4 shows the breakdown of variance of periodontal disease score derived from the path analysis of the offspring generation. It should be noted that the heritability estimate (.217) has too large a standard error (.204) to be of significance. It is concluded from the data that heritability of periodontal disease is negligible, and common family environment is a major determinant of the variation of the condition. -
DISCUSSION
Analysis of our data failed to show the presence of an additive genetic component in the individual variation of the common form of periodontal disease. Theoretically, the failure to reject the null hypothesis of zero heritability could be attributed to the tendency that the sample sizes were consistently underestimated according to the method used here [23], leading to larger type II error. In any event, we can explore the possible magnitude of heritability under another model. Since the estimate of i is very large (.882 + .082), we can set i = 1 and fit the remaining four parameters h, c, k, and z, realizing that the model overestimates h since a larger value for i would lower c (hence elevate h). This leaves no more degrees of freedom to test the goodness of fit of the model, but the variance components can be estimated under the general model. The heritability estimates from this model were .511 + .195 and .064 + .092 for the offspring and parental generations, respectively. The estimate for offspring appears large, but its large standard error vitiates the overestimated value of heritability. Interestingly, the result also supports the proposition that the TABLE 4 COMPONENTS OF VARIANCE ESTIMATED FROM FULL SIB DATA UNDER THE MODEL OF K = 1 AND Z = 0 Proportion of Variance
Component
Genotype (h2) ..217 Common environment (c2) Residual
..383
..400
Total .1.000
Standard Error
.204 .056 .180 ...
PERIODONTAL DISEASE IN HAWAII
81
parental generation has lower heritability than the offspring generation, which is consistent with the finding in human intelligence [23]. Under this model the variance components for common family environment were estimated to be .236 + .047 and .363 + .050 for children and parents, respectively, showing considerable degree of stability. A genetic study on periodontal disease involving intergenerational family members is complicated by association of age with the risk of the disease. An investigator is therefore limited to either studying multiple generation families with only older adults or studying families with little or no age restriction but with statistical adjustment for age differences. The present study took the latter alternative because of the obvious difficulty associated with the first choice under modern social conditions. The adjustment process used both age and age squared terms to remove the age effect as much as possible. Possible effects of age on variances for the two generations cannot be specified precisely. Path analysis with other conditions has demonstrated marked robustness of the method under the condition of considerable departure from homoscedasticity. The finding of insignificant genetic component from this study is in apparent conflict with the earlier observations of the depressing effect of inbreeding [9] and the favorable effect of racial hybridity [8]. However, it must be pointed out that these studies were done on children and hence were largely concerned with gingivitis, which is a mild and reversible symptom of periodontal disease. Our previous study [7] suggested that gingivitis may be characterized in two ways: (1) the condition occurs in association with other destructive signs of the disease as represented by the first principal component, the subject of the present study; and (2) gingivitis is simply an isolated symptom in response to action of bacterial plaque on the tooth as characterized by the second principal component [7]. It is likely that gingivitis, on which the effects of inbreeding and racial hybridity were demonstrated, belonged to the latter class or was of mixed origin. An alternative explanation for the observed inconsistency between this study and the earlier work is that environmental effects associated with inbreeding or hybridity were incompletely removed from the covariance analysis in the earlier studies. The significance of family environment in the etiology of periodontal disease has been clearly demonstrated in the present study. SUMMARY
In order to determine the relative influence of genetic and environmental factors in periodontal disease, path analysis has been applied to 241 nuclear families. Common family environment was represented by an index. The data failed to detect significant heritability, and common family environment proved to be a major determinant in the variation of periodontal health. ACKNOWLEDGMENTS The authors are greatly indebted to the co-investigators of the Behavioral Biology Laboratory of the University of Hawaii, who saw that the subjects of their study on cognitive ability were made available to this study. Professor Yoshi Koga of the Department of Dental Hygiene kindly made their dental facility available to this project. The authors are also grateful to Mrs. Linda Kumasaka and Mrs. Carol Hiraoka, who provided invaluable technical assistance for this study. The assistance of Dr. S. A. Schendel at the initial phase of this study is also appreciated. Mr. Richard Johnson kindly made arrangements to examine some subjects at the Schofield Barracks.
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