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Genetic Variance of Body Mass Index From Childhood To Early Adulthood
Genetic Variance of Body Mass Index From Childhood To Early Adulthood
DOI 10.1007/s10519-011-9486-x
ORIGINAL RESEARCH
Kenneth S. Kendler
Received: 15 April 2011 / Accepted: 13 July 2011 / Published online: 5 August 2011
Springer Science+Business Media, LLC 2011
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Behav Genet (2012) 42:8695 87
much higher than the environmental correlation (\0.67) The aim of the current study is to address these unan-
(Haberstick et al. 2010). In a longitudinal study of Finnish swered questions in the Swedish Twin Registry: Swedish
twins aged 1112, 14, and 17 years, Lajunen et al. (2009) Twin Study of Child and Adolescent Development
found the genetic component was higher in later adoles- (TCHAD).
cence than early adolescence for both males and females.
There was also a higher correlation between the genetic
components over time than the environmental components Methods
(Lajunen et al. 2009). Furthermore, results from this study
suggest common environmental influences are important in TCHAD
early but not later adolescence.
The molecular genetic literature provides further evi- The TCHAD sample has previously been described
dence for stability in genes influencing BMI in childhood (Lichtenstein et al. 2007). Briefly, TCHAD is an ongoing
and adulthood. For example, SNPs in the FTO gene are longitudinal study of 1480 twin pairs born between May
associated with childhood and adult obesity (Frayling et al. 1985 and December 1986. Data were collected when the
2007; Dina et al. 2007). Taken together these studies pro- twins were the following ages: 89; 1314; 1617; 1920
vide some indication that several of the same genetic years. Both twins parent and twin reports are contained in
influences contribute to the variability in BMI across time, these data (Lichtenstein et al. 2007). All data were col-
but environmental influences change from early adolescent lected in accord with the Declaration of Helsinki and all
into adulthood. In fact, common environmental influences research were approved by an institutional review board.
seem important in early adolescents, but not beyond that
developmental stage (Haberstick et al. 2010; Lajunen et al. Zygosity determination
2009).
It has been established that BMI is relatively stable Zygosity determination was based on twin and parental
over time. For example, approximately 70% of obese reports of the similarity of the twins appearances during
adolescents will be obese adults (Parsons et al. 1999). childhood and how often the twins were confused for one
Additional research is needed to help determine if the another as children. To test accuracy of this algorithm;
stability of BMI over time is primarily attributable to zygosity determination was made using 16 DNA poly-
genetic or environmental sources. BMI is influenced by morphisms on 106 same-sex twin pairs. The DNA analysis
biologic factors such as puberty. Puberty is characterized showed the algorithm was 95% accurate (Lichtenstein et al.
by increased hormone levels and rapid growth and 2007).
development. At the time of initial data collect, at least a
portion of participants in both the Haberstick et al. and
Lajunen et al. were likely to have begun puberty, but Measures and current sample
puberty measures were not included in either of these
studies. In another longitudinal study of twins aged BMI
1216, the authors concluded that twins were likely in the
midst of puberty and genetic factors were important in BMI was calculated as weight in kg/height in m2. Height
BMI during puberty; however a direct measure of puberty and weight were reported by the twins parent at waves 13
stage was not used (Cornes et al. 2007). Therefore, and by the twins at waves 24.
additional research is needed to fully understand the
effect of puberty on BMI. Puberty
It is also unknown if parent and twin (child) report of
BMI are similar. Elucidating the concordance between At wave 2, The Pubertal Development Scale (Petersen
these two sources could (1) help determine the accuracy of et al. 1988) was administered to twins parents and twins.
reports; (2) provide information regarding the possibility of Participants were asked five questions regarding each
asking children as young as age 13 about their height and twins physical maturation including: if a height growth
weight; (3) provide information regarding similarities and spurt had occurred; if growth of body hair was present on
difference from longitudinal models using parent or child armpits and genitalia; if skin changes were noticed; if the
reports; and (4) help indicate if reports gathered by parent voice had deepened (males only); if facial hair growth was
and child sources could potentially be used in conjunction present (males only); if breast development was present
with one another for samples in which data were collected (females only); and if menstruation had begun (females
from parents about a child in childhood and the child about only). An algorithm was created to determine puberty
them self in later waves of data collection. stage. If any question had a missing value, puberty status
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88 Behav Genet (2012) 42:8695
was coded as missing. Stages were grouped follows: pre- concordance. The same model was fit for twin report,
pubertal; beginning pubertal; mid-pubertal; advanced however waves 2, 3, and 4 were modeled. Puberty stage
pubertal; and post pubertal. All five puberty stages were was used to regress main effect on the mean BMI at wave 2
used for all models. in both the parent and twin model. Sex limitation and
moderation on the variances was not fit in multivariate
models because of known limitations (Neale et al. 2006).
Statistical methods The five-group (MZ males, MZ females, DZ males, DZ
females, and opposite-sex twins) model was fit; means and
Means [standard deviations (sd)] were calculated for BMI variances were equated across twin order, zygosity group,
at each wave for males and females and are given sepa- male opposite-sex twins were equated with male same-sex
rately for each reporter. The data were checked for outliers twins and female opposite-sex twins were equated with
and individuals with a BMI C 3 standard deviations from female same-sex twin, but based on results from saturated
the mean were considered to be outliers and removed for model comparisons twins were not equated across sex. In
the analyses. Pearsons product-moment correlations were the first model parental reported BMI at waves 1, 2, and 3
performed between parent and twin reported BMI for were entered in that order. In the second model, twin
waves 2 and 3, and Spearmans correlations were per- reported BMI at waves 2, 3, and 4, were entered in that
formed for parent and twin report of puberty at wave 2. order. The models allowed for the main effects of puberty
These correlations were performed separately for males stage to be regressed out of the mean for the respective
and females. BMI variable for wave 2 only; the parent reported puberty
This study was based on the classic twin design and its variable was used in the parent model and the twin reported
assumptions. Mainly, monozygotic twins (MZ) twins share puberty variable in the twin model. Submodels were then
all genes, and dizygotic (DZ) twins share on average half fit removing the effects of puberty status on the means in
their genes. The basic principle behind twin modeling is both the parent and twin model. To determine if genetic
the similarity of MZ twins to that of DZ twins can be variance differed significantly among waves, the genetic
compared. This allows for estimates of the role of genetic variance between two waves at a time were constrained to
and environmental factors. These factors can be divided in equal one another. If a significantly worse fitting model
additive genetic factors (A), common environmental fac- resulted, the parameters differ significantly.
tors (C), and unique environmental factors (E). Measure- To further understand the relationship between puberty
ment error is included in E (Neale and Maes 1998; Neale and BMI, an additional univariate model with puberty
and Cardon 1992). moderation on the means and variances was fit for the twin
For the current study, two Cholesky decomposition report since we believed these puberty data to be most
models were fit. Figure 1 depicts the model fit for parental accurate. This model included an additional parameter to
report of twin 1. Here the direct paths represent the within model qualitative sex differences. All statistical analyses
wave estimates and the cross paths represent the inter-wave were conducted in the R software version 2.12.2 (R
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Behav Genet (2012) 42:8695 89
Development Core Team 2010); all twin modeling was Model fit statistics are contained in Table 3. The full
conducted using OpenMx version 1.06 (Boker et al. 2011). model allowing for the effects of puberty on the BMI
means fit significantly better than the more parsimonious
model without puberty moderation on BMI means; there-
Results fore all reported estimates are from the moderation model.
Parameter estimates and 95% confidence intervals from the
For males, reported BMIs means and parent twin are Cholesky decomposition models are contained in Tables 4,
contained in Table 1 and correlations are presented in 5, 6, 7. Tables 4 and 5 show parent and twin parameter
Table 2. In general, parent-twin correlations in their report estimates for males. The within wave estimates are con-
of twin BMIs were high. As expected, BMI increases over tained on the diagonal, the proportion of phenotypic cor-
time as reported by both parents and twins. relation attributed to each parameter are contained on the
At wave 2, the majority of twins had begun puberty, but lower off diagonal, and the genetic and environmental
had not fully matured. As expected, overall females were at correlations are contained on the upper off diagonal.
later stages of puberty than males. Male pubertal stages are The heritability estimates increased across waves with
as follows: prepubertal, 228 (parent), 101(twin); beginning the largest increase coming between waves 1 and 2; this
pubertal, 345(parent), 443 (twin); mid-pubertal 381 (par- resulted from the parent reported model. Table 8 indicates
ent), 468 (twin); advanced pubertal 52 (parent), 46 (twin). genetic variance differed significantly between waves in
There were no post pubertal males by either parent or twin the parent model, but in the twin model genetic variance
report. The parent-twin correlation for pubertal status was was not significantly different across waves. Following
moderate (0.70). Pubertal status reported for females are as childhood, the genetic parameter was responsible for over
follows: beginning pubertal 1 (parent), 5 (twin); mid- 60% of the variance in BMI. Looking at both the parent
pubertal 716 (parent), 736 (twin); advanced pubertal 342 report and twin report models, genetic sources accounted
(parent), 356 (twin). There were no females reported as for 67%-83% of the correlation in BMI across waves. The
pre-pubertal or post pubertal. Parent twin correlation for common environment became less important over time and
female puberty stage was high (0.94). accounted for under 30% of the phenotypic the correlation
Parent report BMI wave 1 0.83 (0.780.87) 0.89 (0.860.92) 0.59 (0.460.69) 0.64 (0.520.73) 0.48 (0.390.57)
Parent report BMI wave 2 0.87 (0.830.90) 0.86 (0.820.89) 0.45 (0.300.58) 0.59 (0.470.69) 0.39 (0.280.49)
Twin report BMI wave 2 0.85 (0.800.89) 0.87 (0.830.90) 0.43 (0.260.57) 0.44 (0.300.57) 0.29 (0.170.40)
Parent/twin BMI correlation wave 2 0.95 (0.940.96) 0.95 (0.940.96) 0.95 (0.940.96) 0.92 (0.900.94) 0.90 (0.880.92)
Parent report BMI wave 3 0.81 (0.750.86) 0.88 (0.830.91) 0.38 (0.200.53) 0.42 (0.250.56) 0.22 (0.080.34)
Twin report BMI wave 3 0.70 (0.620.77) 0.83 (0.780.87) 0.37 (0.220.51) 0.43 (0.290.55) 0.25 (0.140.36)
Parent/twin BMI correlation wave 3 0.84 (0.800.87) 0.92 (0900.94) 0.87 (0.830.90) 0.90 (0.870.92) 0.88 (0.860.90)
Twin report BMI wave 4 0.73 (0.630.81) 0.75 (0.680.81) 0.41 (0.180.59) 0.36 (0.200.52) 0.16 (0.010.32)
Parent puberty stage report wave 2 0.72* 0.95* 0.67* 0.94* 0.86*
Twin puberty stage report wave 2 0.91* 0.76* 0.51* 0.38* -0.39*
Parent/twin puberty stage correlation 0.68* 0.72* 0.30* 0.26* -0.31*
Spearmans correlations do not yield 95% confidence intervals
MZM monozygotic twin male, MZF monozygotic twin female, DZM dizygotic twin male, DZF dizygotic twin female, OS opposite sex twin,
BMI body mass index
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Table 3 Cholesky
Parameters -2LL df AIC D-2LL Ddf p-Value
decomposition model
fit statistics Full parent moderation model 44 16631.99 4361 7909.99
Parent model no moderation 42 16655.85 4363 7929.85 23.86 2 0
-2LL -2 log-likelihood, Full twin moderation model 44 19076.86 4679 9718.86
df degrees of freedom, Full twin model no moderation 42 19084.55 4681 9722.55 7.69 2 0.02
AIC Akaike information criteria
across time. The unique environmental parameter became kg/m2 in prepuberty and 19.1 kg/m2 in mid-puberty. In
more important over time, but did not contribute strongly females, the total variance became greater with increasing
to the cross-time correlation of BMI. maturity (Fig. 2c). As shown in Fig. 2d, the variance in
Parent and twin results for females are contained in BMI explained by genetic factors ranged from 0.82 (95%
Tables 6 and 7. Similar to males, the heritability estimates CI: 0.590.89) in mid-puberty to 0.91 (95% CI: 0.480.95)
increased over time, but the largest increases were seen in advanced puberty; the variance explained by C ranged
between waves 2 and 3 in both the parent report and twin from 0.05 (95%CI: 0.000.27) to 0.02 (95% CI: 0.000.45)
report models; Table 8 indicates that genetic variance and that of E ranged from 0.14 (95%CI: 0.100.18) to 0.07
increased significantly across waves in the parent model, (95%CI: 0.040.12). All five puberty stages for males and
and increased between waves 2 and 4 in the twin model, females were entered into the this model, but given the
with waves 2 and 3 bordering on differing significantly. In small number of males in advanced puberty and the small
childhood, genetic factors accounted for over 50% of the number of females in beginning puberty we do not report
variance in BMI and in late-adolescents and early adult- these values.
hood, genetic factors accounted for over 65% of the vari-
ance in BMI. Genetic factors were responsible for 51% of
the correlation in BMI between wave 1 and wave 2 in the Discussion
parental report model and 78% of the correlation in BMI
between wave 3 and wave 4 in the twin report model. Also The current study provides additional information about
similar to males, the common environment became less the BMI phenotype. For waves 2 and 3, relatively similar
important over time, however this parameter contributed patterns are seen in parental and twin reports in males and
more strongly to the correlation in BMI across time in females and correlation between BMI for parent and twin
females. The unique environmental parameter followed the reports were quite high. The 95% CI in the parent and child
same pattern in females as males and increased in magni- models overlap and, with the exception of wave 3 param-
tude over time. eter estimate for E in males, the point estimates of the
Puberty stage was used to regress out the mean effect of parent model is contained in the 95% CI of the child model
puberty on the BMI means at wave 2 in both the parent and and the point estimates of the child model is contained in
twin models. The parent model yielded a b coefficient of the 95% CI of the parent model. The results of the current
pubertal stage on BMI of 0.17 for males and -0.53 for study expand results of previous investigations (Haberstick
females. For the child model, the b coefficient for males et al. 2010; Lajunen et al. 2009) by providing additional
was -0.0004 and 0.00003 for females. Removal of puberty information regarding the proportion of phenotypic corre-
moderation for both the parent and twin models resulted in lation across time which can be attributed to genetic and
significantly worse fitting models (Table 3). environmental sources, providing information regarding
In the univariate analysis, the correlation between the parent/twin correlation of BMI, and indicate the impor-
male and female genetic influences on BMI was 0.87 [95% tance of puberty stage on BMI variance. This information
confidence interval (CI): 0.111.00]. This suggests that can help further the understanding of developmental fac-
overall at wave 2 males and females share 87% of genes tors which influence BMI.
responsible for variance in BMI. Total variance in males Inter-rater reliability and consistency is often of great
was lower with increasing maturity (Fig. 2a). In males, the concern. In the current study, the correlations between
variance in BMI explained by the genetic component ran- parent and twin report were moderate to high. In addition,
ged from 0.32 (95% CI: 0.100.71) in prepuberty to 0.87 the parameter estimates for parent and twin report were
(95% CI: 0.730.93) in mid-puberty and the variance in comparable as indicated by overlapping confidence inter-
BMI explained by the C parameter ranged from 0.63 (95% vals. This indicates that during the adolescent years,
CI: 0.230.86) in prepuberty to 0.03 (95% CI: 0.000.17) obtaining BMI information from parent or child is likely to
in mid-puberty. The variance explained by the unique yield similar results and are therefore roughly equivalent.
environmental component was relatively stable across This suggests that BMI collected from either reporter at
puberty stages (Fig. 2b). The mean value of BMI was 18.4 this age is likely acceptable for use in research studies and
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Table 4 Parental report male parameter estimate (95% confidence interval) for body mass index across waves
Wave 1 Wave 2 Wave 3 Wave 1 Wave 2 Wave 3 Wave 1 Wave 2 Wave 3
a2 a2 a2 c2 c2 c2 e2 e2 e2
Behav Genet (2012) 42:8695
Wave 1 0.42 (0.260.62) 0.82 (0.610.98) 0.74 (0.520.91) 0.43 (0.230.58) 0.52 (0.190.81) 0.73 (0.261.00) 0.15 (0.120.20) 0.24 (0.060.40) 0.14 (-0.070.33)
Wave 2 0.67 (0.480.87) 0.62 (0.480.77) 0.78 (0.680.89) 0.28 (0.080.46) 0.25 (0.110.40) 0.96 (0.561.00) 0.05 (0.010.10) 0.12 (0.100.16) 0.37 (0.170.53)
Wave 3 0.68 (0.430.91) 0.69 (0.510.88) 0.70 (0.540.82) 0.29 (0.070.51) 0.24 (0.070.42) 0.13 (0.020.29) 0.04 (-0.020.10) 0.07 (0.030.12) 0.17 (0.130.22)
Note: a2 heritability component, c2 common environment component, e2 unique environment component, within wave estimates are on the diagonal, proportion of BMI correlation across time
attributed to each parameter are on the lower off diagonal, and parameter correlation on the upper off diagonal
Table 5 Twin report male parameter estimate (95% confidence interval) for body mass index across waves
Wave 2 Wave 3 Wave 4 Wave 2 Wave 3 Wave 4 Wave 2 Wave 3 Wave 4
a2 a2 a2 c2 c2 c2 e2 e2 e2
Wave 2 0.72 (0.550.86) 0.94 (0.841.00) 0.78 (0.280.92) 0.15 (0.020.32) 0.79 (-1.001.00) 1.00 (-1.001.00) 0.13 (0.100.17) 0.19 (0.020.35) 0.15 (-0.080.36)
Wave 3 0.83 (0.630.99) 0.64 (0.450.77) 0.92 (0.831.00) 0.13 (-0.020.31) 0.10 (0.000.28) 0.75 (-1.001.00) 0.05 (0.000.09) 0.26 (0.210.32) 0.37 (0.230.49)
Wave 4 0.81 (0.580.98) 0.79 (0.580.92) 0.68 (0.470.79) 0.16 (0.000.37) 0.09 (-0.030.29) 0.08 (0.000.27) 0.04 (-0.020.10) 0.12 (0.070.18) 0.24 (0.190.32)
Note: a2 heritability component, c2 common environment component, e2 unique environment component, within wave estimates are on the diagonal, proportion of BMI correlation across time
attributed to each parameter are on the lower off diagonal, and parameter correlation on the upper off diagonal
91
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Table 6 Parental report female parameter estimate (95% confidence interval) for body mass index across waves
Wave 1 Wave 2 Wave 3 Wave 1 Wave 2 Wave 3 Wave 1 Wave 2 Wave 3
a2 a2 a2 c2 c2 c2 e2 e2 e2
Wave 1 0.56 (0.400.71) 0.76 (0.620.88) 0.48 (0.300.63) 0.33 (0.180.49) 0.61 (0.360.83) 0.68 (0.230.95) 0.11 (0.090.14) 0.34 (0.190.48) 0.26 (0.060.43)
Wave 2 0.51 (0.270.74) 0.42 (0.260.61) 0.61 (0.230.95) 0.41 (0.190.64) 0.42 (0.240.57) 1.00 (0.821.00) 0.08 (0.040.13) 0.16 (0.130.21) 0.47 (0.320.59)
Wave 3 0.63 (0.360.87) 0.57 (0.380.76) 0.72 (0.570.84) 0.31 (0.080.57) 0.34 (0.150.53) 0.15 (0.040.30) 0.06 (0.020.12) 0.09 (0.060.13) 0.13 (0.100.16)
2 2 2
Note: a heritability component, c common environment component, e unique environment component, within wave estimates are on the diagonal, proportion of BMI correlation across time
attributed to each parameter are on the lower off diagonal, and parameter correlation on the upper off diagonal
Table 7 Twin report female parameter estimate (95% confidence interval) for body mass index across waves
Wave 2 Wave 3 Wave 4 Wave 2 Wave 3 Wave 4 Wave 2 Wave 3 Wave 4
a2 a2 a2 c2 c2 c2 e2 e2 e2
Wave 2 0.55 (0.370.75) 0.86 (0.770.95) 0.85 (0.740.99) 0.30 (0.100.47) 1.00 (0.801.00) 1.00 (0.561.00) 0.15 (0.120.19) 0.44 (0.310.56) 0.17 (0.030.32)
Wave 3 0.65 (0.450.86) 0.68 (0.510.81) 0.87 (0.810.94) 0.26 (0.060.46) 0.14 (0.020.31) 1.00 (0.631.00) 0.09 (0.060.13) 0.18 (0.140.22) 0.26 (0.120.38)
Wave 4 0.72 (0.500.92) 0.78 (0.590.92) 0.69 (0.520.80) 0.24 (0.050.45) 0.16 (0.020.34) 0.11 (0.010.27) 0.04 (0.000.08) 0.06 (0.030.10) 0.21 (0.160.26)
2 2 2
Note: a heritability component, c common environment component, e unique environment component, within wave estimates are on the diagonal, proportion of BMI correlation across time
attributed to each parameter are on the lower off diagonal, and parameter correlation on the upper off diagonal
Behav Genet (2012) 42:8695
Behav Genet (2012) 42:8695 93
is likely subject to the same pitfalls of other self-reported The heritability estimates of the current study are similar
BMI data. Given the similarities between parent and twin to those in previous reports (Stunkard et al. 1986; Allison
report and the similarities in longitudinal analysis of parent et al. 1996; Maes et al. 1997). However, the current study
and twin report, it may be possible to combine these reports indicates that the genetic component in BMI is lower in
into a single model as twins age if additional data are childhood (prepuberty) and increases in early adolescents
collected. However, inter-rater consistency may not gen- after which time it remains relatively stable. The largest
eralize beyond this phenotype. For example, the parent- change in factors associated with the variance in BMI
male twin report of puberty status did not yield nearly as comes between waves 1 and 2 for males and 2 and 3 for
high correlation as any of the parent/twin BMI correlations. females suggesting both sex differences and the importance
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94 Behav Genet (2012) 42:8695
of puberty on the heritability of BMI. As expected, com- results may not generalize beyond twins born in Sweden
mon environmental influences which were prominent in between 1985 and 1986.
childhood approach having no influence on the variance of
BMI in early adulthood and the unique environmental
influences increase over time. The relative importance of Conclusion
genetic factors increases with age indicated by the rela-
tively high and increasing proportion of BMI correlation High parent-twin correlations in BMI suggest that data
attributed to genetic sources across time. collection from either report is likely equally appropriate
In univariate analyses of twin report at wave 2, we for use in research studies and likely to give the similar
examined the influence of puberty stage on BMI means and results. Genetic factors are largely responsible for BMI
variances. As puberty stage becomes more advanced, the correlation across time and may help to explain the diffi-
genetic component contributes more strongly to the vari- culty of altering weight and maintaining weight loss. The
ance in BMI. This illustrates that puberty is plausibly importance of puberty stage on factors that effect BMI
involved in the increasing importance of genetic factors variance is confirmed by univariate models; steep increases
and decreasing importance of common environmental occur in the magnitude of the genetic component of BMI
factors involved in BMI variance. In early adolescence, during puberty.
many of the same genes appear to be responsible for BMI
variance in males and females. The actual estimation of Acknowledgments We would like to thank Swedish Council for
Working Life and Social Research and the Swedish Research
this parameter indicates that 87% of the genes were the Council. Dr. Dellava was funded by NIMH T32MH20030 (PI:
same; this was not significantly different from unity. Michael C. Neale) and 5R37DA018673 (PI: Michael C. Neale). We
Therefore, during puberty males and females share the would also like to thank all the participants who made this study
majority of the genetic factors responsible for BMI possible.
variance.
Limitations References
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