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Contributions to variance in phalangeal growth Estimates from twins.

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Contributions to Variance in Phalangeal Growth:
Estimates from Twins
RONALD K. WETHERINGTON AND GARY W. RUTENBERG
Department ofAnthropology, Southern Methodist Uniuersity, Dallas, Texas, 75275
KEY WORDS Twins. Bone growth
. Hand-wrist . Genetics
ABSTRACT
Lengths of the second metacarpal and fourth middle phalanx of a
sample of 99 sets of radiographs of twins (45 MZ sets and 54 like-sex DZ sets) are
subjected to variance analysis. The purpose is to examine incremental growth
status between the appearance of these bones and the fusion of their epiphyses.
Grouped data show higher F-ratios and H scores for males in MC2 length and for
females in MP4 length. When the data are sub-divided by age (10 and under,
older than 101,the later ages show uniformly higher F and H scores than the
younger, and males higher than females for all measurements. I t is suggested
that the influence of the environment is relatively less in later ages, and that Xchromosomal influence plays a part in determining tubular bone growth in the
hand-wrist.
Variation in osseous development in the
hand and wrist has been the subject of several
studies to assess the relative genetic and
environmental influences on growth. Both the
timing (Garn e t al., '61b; Garn e t al., '63) and
sequence (Hertzog, et al., '69) of hand-wrist
centers have revealed evidence of genetic control, as have both the timing and sequences of
epiphyseal union in the metacarpals and phalanges (Garn e t al., '61a).
The process and rate of incremental growth
intervening between the appearance of osseous centers and their epiphyseal fusion have
not been adequately studied with respect to
genetic control. In light of the absence of demonstrable correlation between the earlier
and later episodes of hand growth, such an investigation is important.
The most valid means of estimating the contributions to bone growth of genotype and
environment, relative to one another, is the
comparison of monozygous and like-sex dizygous twins. While for discrete variables concordance studies are appropriate, for continuous variables such as incremental growth
other methods must be applied. Since variation in incremental growth is the result of
both genotype and environment (and their interaction), applicable methods of analysis
seek to partition t h a t portion of total variance
AM. J. PHYS. ANTHROP. (1978)48: 83-88.
due to environmental variance and that due to
genetic variance.
Commonly used analysis of variance (anova) tests are the F-ratio and Holtzinger's heritability index (h2)with various modifications
(Holzinger, '29; Cavalli-Sforza and Bodmer,
'711. While anova in general and heritability
in particular have been criticized for having
been both misapplied and misinterpreted
(Feldman and Lewontin, '75; Layzer, '74; Sanday, '72), their proper application can provide
valid estimates of the relative genotypic-environmental contributions to observed phenotypic variation.
METHODS AND MATERIAL
In a n effort to clarify these proportionate
contributions to growth variance in the hand,
we applied anova to metacarpal and phalangeal dimensions in a twin sample. The
subjects were drawn from the longitudinal
Nebraska Child Growth Study conducted from
1958 through 1964. The collection of handwrist radiographs represents 469 children
(226 males, 243 females) with a total agerange of 2 to 19 years. Included in the study
are 102 sets of like-sex twins, all Caucasian
and all raised by their natural families. General medical histories on each child, listing
episodic illness, were collected during the
83
84
RONALD K. WETHERINGTON AND GARY W. RUTENBERG
study. We thus have an opportunity to examine growth processes in children with apparently adequate nutritional backgrounds
and in general good health.
The study is based on 99 pairs of like-sex
twins who participated in the 12-month recall
examination for periods ranging from one to
seven years: 47 pairs of male and 52 pairs of
female twins. Among the males, 27 pairs were
classified as dissimilar and 20 pairs as similar;
and among the females, 27 pairs as dissimilar
and 25 as similar. Thus, of the total of 99 pairs,
54 (108 individuals) may be classified as
dizygous and 45 (90 individuals) as monozygous, both terms being approximate.
Zygosity was estimated by parent-child and
within-pair comparisons which included blood
grouping (ABO, Fy, K, Le), surface morphology of the mandibular first molar, cephalometry, several postcranial anthropometrics, and
overall morphological similarities. The distributions of zygosity by sex does not depart
from random expectation (x' = 0.303, p >
0.005). While recognizing the possibilities of
misclassification, the categories MZ and DZ
will be used here.
Measurements on radiographs used for the
present study include lengths of the second
metacarpal (MC 2) and the middle fourth phalanx (MP 4). Measurements were taken a t
mid-line of the diaphysis and included the
epiphysis and intervening cartilage plate. All
measurements were made with a Helios x-ray
caliper and recorded to the nearest 0.1 mm.
The choice of MC 2 and MP 4 was based on
the high communalities these display in incremental growth (Roche and Hermann, '70a,b)
and the utility of these bones in helping to
assess other growth components (cortical
thickness and density in MC 2, brachymesophalangia in MP 5-MP 4 comparisons).
For each twin-pair, measurements were recorded for each radiograph in the longitudinal
study, amounting to 243 pairs of radiographs.
For the current study, only the first films of
each twin-pair were used, totalling 99 pairs of
radiographs. Longitudinal aspects of the collection are being treated elsewhere (Wetherington and Rutenberg, in preparation).
FINDINGS
Two procedures were used for initial data
reduction: First, the initial radiographs of
each twin-pair were selected and grouped
according to sex and zygosity. Intra-pair
means, variances and correlations were calculated for each group. From these results, Fratios' and heritability indices' were obtained. The heritability scores, with their
standard errors, were calculated separately
using variance and mean r . Results are indicated in table 1. In this paper H refers to the
heritability calculation from variance in bone
lengths, and H' refers to the calculation from
correlation coefficients.
Secondly, to evaluate the effects of age on
the intra-pair variances, and particularly to
separate pre-pubertal from pubertal effects,
the data were separated by age-groups and
again classified according to sex and zygosity.
The same statistics were applied t o these data
(table 2). Small cohort sizes prevented us from
using 5-year intervals for the age-grouping.
We therefore chose two cohorts, ages 2-10 representing the pre-pubertal portion of growth
in the hand, and ages 11-19 representing that
portion influenced by pubertal changes.
In the grouped data, for both MC 3 and MP 4
lengths, within-pair variances are lower for
MZ than for DZ twins, as expected under the
genetic hypothesis. Likewise, the intra-pair
correlations (r) are higher for MZ than for DZ
twins. For MZ pairs, correlations for males
and females are not significantly different,
and are equivalent for both MC 2 and MP 4
lengths. However, for DZ intra-pair correlations females rank slightly higher than males
for MC 2 lengths (r = 0.97 and 0.93, respectively), while males rank higher than females
for MP 4 lengths (r = 0.94 and 0.86, respectively). All intra-pair correlations for the
grouped age data are significant (p < 0.001).
When the sample is divided by age into
the pre-pubertal and pubertal/post-pubertal
groups, influences of age on the growth process become apparent, despite the possibly
misleading results due to some of the low
numbers of pairs. Intra-pair variances among
MZ males are higher in the earlier age category for both MC 2 and MP 4 lengths, and among
DZ males are lower in the earlier age category
1 V,V2 = F.05 (vl,vs),where V, is intra-pair DZ variance and V1 is
intra-pair MZ variance.
VMZ . variance for each twin-group was calculated by
=
vDz ' the formula V = iZdiz, where di is the difference between twin A and twin B of a p%r.This is the unbiased variance estimator when the population mean difference is known to be
equal to zero. The variance of H, or its standard error, was calculated
after the method in Cavalli-Sforza and Bodmer ('71).
c1 -'MP). 'MZ2 is the squared product-moment correHo=
(1 - r ~ z z )' lation coefficient for munozygous twins.
and WZzis the same fur dizygous twins.
85
PHALANGEAL GROWTH IN TWINS
TABLE 1
Variance comparisons for twin sample: grouped data
Twin type
MZ males
DZmales
MZ females
DZfemales
MZ males
DZmales
MZ females
DZfemales
?j
Pairs
Bone
20
27
25
27
MC2
MC2
20
27
M
MP
P4
4
25
MP4
MP4
27
MC2
MC2
Intra-pair
variance
r
0.0146
0.1764
0.0169
0.0671
0.988
o.9323
0.986
o,9683
0.0058
0.0243
0.0035
0.0524
o.8633
0.984
::::::
H1
Standard
error
H' 2
0.92
20.002
0.82
12.0823
0.75
20.013
0.56
3.9703
0.76
20.013
0.45
0.93
+0.001
0.875
14.971
F
F
4.1903
TABLE 2
Variance comparisons for twin sample by age categories
Twin pair
N
pairs
Bone
17
15
18
14
17
15
18
14
MC2
MC2
MC2
MC2
Intra-pair
variance
r
A
Standard
error
H'
0.86
rtO.009
0.93
7.462
0.58
t0.340
0.65
1.245
0.755
t0.112
0.70
2.086
0.97
?0.001
0.94
20.324'
20.002
1.000
22.326
20.017
0.931
7.043
Ages 2-10
MZ males
DZ males
MZ females
DZ females
MZ males
DZ males
MZ females
DZ females
MP4
MP4
MP4
MP4
0.0151
0.1129
0.0146
0.0182
0.0066
0.0137
0.0037
0.0756
O""
'
0.689'
:::;::
:::::'
Ages 11-19
DZfemales
MZ males
DZ males
MZ females
DZ females
13
3
12
7
13
MC2
MP4
MP4
MP4
MP4
0.1232
0.0016
0.0357
0.0027
0.0190
08002
u.8"
1.000
o,712
0.97
:::!;: 0.87
' po.01.
2
p 0.001
for both bones. However, intra-pair variances
for both MZ and DZ females are lower in the
earlier age category for MC 2 length and in the
later age category for M P 4 length.
For the intra-pair correlations, DZ females
show a higher values for MC 2 in the earlier
age category and are higher for M P 4 in the
later age category. The correlation for M P 4
length in the earlier ages for females (r =
0.04) is the lowest of all values obtained and
the only one showing no significance. The DZ
males show the opposite age-relationship,
with higher correlation for MC 2 in the later
ages and for MP 4 in the earlier ages.
These differences are reflected, obviously,
in the F-ratios and H indices, and thus aid in
their interpretation. The F-ratios for the
grouped data are all significant (p < 0.001),
but are higher among males for MC 2 lengths
and higher among females for M P 4 lengths.
The same is true for the heritability scores,
with both MC 2 lengths for males and MP 4
lengths for females higher than the H scores
for MC2 lengths in females (H = 0.75) and
MP 4 lengths in males (H = 0.76).Heritability indices based on the intra-pair correlations
are lower overall, but reflect the same relative
values.
86
RONALD K. WETHERINGTON AND GARY W. RUTENBERG
When the data are age-grouped, the F-ratio
is higher for later than for earlier ages in both
sexes for MC 2 lengths and higher in males for
M P 4 lengths. I t is higher in females, however,
in the earlier ages for M P 4 lengths. The H
scores show the same age-related changes: increasing heritability values with increasing
age for males and females, and for both MC 2
and MP 4 lengths, except for M P 4 length in
females. When H' is computed on the squared
intra-pair correlations, the scores for earlier
and later ages for MP 4 lengths in females are
essentially the same.
DISCUSSION
Interpretation of the anova calculations in
this study depends upon the validity of
assumptions made regarding both zygosity
and the heritability of continuous traits. The
assumption that the MZ and DZ classifications are accurate is supported, but nevertheless not fully verified, by both the blood-group
data and the uniformly lower within-pair variances for the group classified as monozygous.
The assumptions underlying heritability
and the definition of the genetic portion of
phenotypic variance have been subject to a
great deal of discussion. These include the
assumptions: (1) that there is a uniform distribution of the underlying genotypes across
environments; that is, the correlation of environment with genotype is no different from
the MZ group than for the DZ group, and (2)
that the genotype-environment interactions
are of equivalent phenotypic significance for
both MZ and DZ twins.
There is evidence (Osborne and DeGeorge,
'59) that the first assumption is not validthat a t least some environmental components
are more similar for MZ pairs than for DZ
pairs. To the extent that such components include those affecting growth, genotypic contribution to variance will be overestimated by
present methods.
While we believe that these twin study limitations are more relevant to psychological
than to anthropometric measurements there
is a need for more thorough documentation of
the evidence.
If we assume that the within-pair variance
in the MZ group is environmental (because of
identical genotypes), the DZ portion not explained by the MZ variance is presumed to reflect the genetic contribution to that (DZ) variance.
The H index reflects the difference in the
contribution of genotype to phenotypic variance relative to the contribution of environment to phenotypic variance: the score will increase as either environmental or genotypic
variances among dizygous twins increase. The
F-ratio establishes statistical probability and
reliability for this variance comparison. The
value of using the H statistic here, then, lies
in providing a numerical percentage indicating the ratio of the environmental-genetic
contribution to observed phenotypic variation.
Such values apply only to the population sample in the present study.
The H values are apparently not stable
through time. With the exception of M P 4
lengths among females, the values are higher
for the older age group than for the pre-pubertal group, suggesting a decreasing environmental influence on variability through time
for these phenotypes, contrary to previous
conclusions (Vandenberg, '62). Since the two
age-groups consist of different twin-pairs, the
possibility of relative differences in genotypes
influencing the observed values cannot be
ruled out, but is unlikely in view of the consistency of the value differences. The incorporation of the longitudinal films should clarify
this possibility, and preliminary data support
the hypothesis of reduced relative environmental contribution with increasing age.
Also significant is the fact that the H values
for males in the later age-group are significantly higher than for females, and with the
exception of MP 4 lengths, also higher in the
earlier age-group. The degree to which postfusion growth status affects these age differences is not easily interpreted from these
data due to small sample sizes. Osborne and
DeGeorge ('59) included only post-adolescents
for their study, and for both hand length and
middle finger length show higher F ratios for
males. Their computed H scores for middle
finger length (males = 0.87, females = 0.74)
are similar to our results.
This supports a growing body of evidence for
X-Chromosomal influence on osseous development (Garn and McCreery, '70; Garn et al.,
'63; Garn e t al., '69). Since female DZ twins
share identical paternal X chromosomes, each
X-linked genotype for a twin-pair has one
allele in common, reducing the genotypic variance of DZ females relative to DZ males. If
any such genotypes contribute to epistatic influence on bone growth, inter-group phenotypic differences (MZ-DZ)for females will be less
than that for males. This will result in lower
PHALANGEAL GROWTH IN TWINS
F-ratios and H scores in the intra-pair comparisons, as in the study. The fact that this is
not indicated in the earlier age-group for MP 4
length may further indicate relatively higher
environmental influence prior to puberty.
Pending further and broader analysis, then,
two conclusions may tentatively be drawn for
the present population sample: (1) The relative contributions of genotype and environment to variance in MC 2 and MP 4 lengths
change through time, reflecting decreased
environmental influence on final phenotype;
(2) There is in general a greater inter-group
difference between MZ and DZ males than between MZ and DZ females. A possible explanation for this is that for MC 2 and MP 4 lengths,
interim incremental growth between appearance and fusion is partially under the influence of x-linked loci.
In a continuing study, longitudinal films for
available twin-pairs are being age-standardized and analyzed for heritability in rates of
change.
ACKNOWLEDGMENTS
We wish to thank Doctor Harold J. Hietala,
Department of Anthropology and Statistics,
Southern Methodist University, for his helpful suggestions in the statistical applications,
and Doctor Edward I. Fry for making available the data from the Nebraska study.
LITERATURE CITED
Cavalli-Sforza, L. L., and W. F. Bodmer 1971 The Genetics
of Human Populations. W. H. Freeman, San Francisco.
87
Feldman, M. W., and R. C. Lewontin 1975 The heritability
hangup. Science, 190: 1163-1168.
Garn, S. M., and L. D. McCreery 1970 Variability of postnatal ossification timing and evidence for a “dosage” effect.
Am. J. Phys. Anthrop., 32: 139-144.
Garn, S. M., C. G. Rohmann and B. Apfelbaum 1961a Complete epiphyseal union of the hand. Am. J. Phys. Anthrop., 19: 365-372.
Garn, S. M., C. G. Rohmann, and M. Robinow 1961b Increments in hand-wrist ossification. Am. J. Phys. Anthrop.,
19: 45-54.
Garn, S. M., C. G. Rohmann, and A. A. Davis 1963 Genetics
of hand-wrist ossification. Am. J. Phys. Anthrop.,21: 3340.
Garn, S. M., C. G. Rohmann and K. P. Hertzog 1969 Apparent influence of the X chromosome on timing of 73
ossification centers. Am. J . Phys. Anthrop., 30: 123-128.
Hertzog, K. P., F. Falkner and S. M. Garn 1969 The genetic
determination of ossification sequence polymorphism.
Am. J. Phys. Anthrop., 30: 141-144.
Holzinger, K. 1929 The relative effect of nature and nurture in influences on twin differences. J. Educ. Psychol.,
20: 241-248.
Layzer, David 1974 Heritability analyses of IQ scores: science or numerology? Science, 183: 1259-1266.
O s brne , R. H., and F. V. DeGeorge 1959 Genetic Basis of
Morphological Variation; an evaluation and application
of the twin study method. Harvard University Press,
Cambridge.
Roche, A. F., and R. F. Hermann 1970a Association between the rates of elongation of the short bones of the
hand. Am. J. Phys. Anthrop., 32: 83-88.
1970b Rates of change in width and length-width
ratio of the diaphyses of the hand. Am. J. Phys. Anthrop.,
32: 89-96.
Sanday, P. R. 1972 On the causes of IQ differences between
groups and implications for social policy. Human Org., 31:
411-424.
Vandenberg, S. G. 1962 How “stable” are heritability estimates? A comparison of heritability estimates from six
anthropometric studies. Am. J. Phys. Anthrop., 20: 331338.
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