BASIC SCIENCE ARTICLE OPEN
Gene ic egula ion o body size and mo phology om
adolescence o ea ly adul hood
Ka i Sil en oinen
1
✉, Robe F. K uege
2
, Aline Jelenko ic
3
, Reijo Sund
4
, Glenn I. Roisman
5
, Jaakko Kap io
6
and Ma McGue
2
© The Au ho (s) 2025
BACKGROUND: We analyzed he sha ed gene ic backg ound o ex ensi e an h opome ic measu emen s, de e mining body size
and mo phology.
METHODS: An h opome ic measu emen s we e aken o 15 ai s om 1512 US wins a an a e age age o 11.7 yea s (Minneso a,
51% emales) and o 20 ai s a an a e age age o 14.8 yea s o males (N=624) and 18.1 yea s o emales (N=505). Gene ic win
modeling was u ilized o es ima e he gene ic co ela ions be ween hese ai s.
RESULTS: In mid o la e adolescence, high gene ic co ela ions we e ound wi hin heigh - ela ed ai s and oo leng h (
A
=
0.58–1.00) as well as wi hin adiposi y- ela ed ai s (
A
=0.70–0.96), excep o skin old hicknesses. Gene ic co ela ions o
c anio acial measu emen s we e smalle (
A
=0.26–0.80). Howe e , almos all ai s showed some gene ic co ela ions wi h o he
ai s, mos o which we e a leas mode a e (
A
> 0.30). Resul s om ea lie assessmen s in ea ly adolescence wi h ewe ai s bu a
la ge sample size we e la gely simila . Gene ic co ela ions be ween he ini ial and ollow-up assessmen s we e high (
A
=
0.68–0.95), excep o c anio acial ai s, which showed somewha lowe co ela ions (
A
=0.40–0.87).
CONCLUSIONS: Sha ed gene ic a ia ion plays a significan ole in human body size and mo phology as well as hei de elopmen
du ing adolescence.
Pedia ic Resea ch; h ps://doi.o g/10.1038/s41390-025-04259-8
IMPACT:
●The e a e clus e s o an h opome ic ai s showing high gene ic co ela ions.
●The highes gene ic co ela ions we e ound wi hin heigh - and adiposi y- ela ed ai s.
●Nea ly all an h opome ic ai s sha e some gene ic a ia ion.
●Gene ic ac o s impo an ly con ibu e o he g ow h o all ai s du ing adolescence.
●Pleio opic e ec s a e impo an o unde s anding he gene ic egula ion o human physique.
INTRODUCTION
An h opome ic measu emen s a e an essen ial pa o child
heal h check-ups, as abno mal alues can signal p oblems anging
om inadequa e nu i ion
1
o se ious heal h condi ions.
2
Unde -
s anding he gene ic egula ion o g ow h is impo an o
iden i ying en i onmen al and medical issues ha may hinde
heal hy de elopmen . Ex ensi e win and genome-wide associa-
ion (GWA) s udies ha e e ealed significan associa ions o
gene ic ac o s wi h heigh
3,4
and BMI a ia ion.
5,6
Addi ionally,
gene ic influences ha e also been shown o o he an h opo-
me ic ai s, such as wais
7
and ches ci cum e ence,
8
skin old
hicknesses,
9
and c anio acial measu emen s.
10
The same gene ic
ac o s la gely influence heigh and BMI h oughou childhood
and adolescence,
11
and he ole o gene ic ac o s has also been
demons a ed o he de elopmen o head
12
and ches
ci cum e ence.
8
While p e ious s udies ha e highligh ed he
impo ance o gene ic ac o s in g ow h, mos ha e ocused on
heigh and BMI. E idence o many an h opome ic ai s is s ill
lacking, pa icula ly in e ms o longi udinal change.
Despi e ex ensi e gene ic esea ch on an h opome ic ai s,
less is s ill known abou hei sha ed gene ic backg ound. Ea ly
s udies ha e iden ified co ela ion pa e ns among a ious
an h opome ic ai s,
13
sugges ing pa ially co ela ed gene ic
componen s ha a ec di e en body pa s. La e win s udies
ha e ound gene ic co ela ions be ween BMI and wais ci cum-
e ence
7
as well as skin old hicknesses.
14,15
Some gene ically
in o ma i e s udies ha e also explo ed gene ic co ela ions among
a la ge numbe o an h opome ic ai s. S udies using wo-
gene a ion amily da a om ou popula ions (one om India and
h ee om Eu ope) ound mode a e gene ic co ela ions be ween
Recei ed: 2 Decembe 2024 Re ised: 10 Ap il 2025 Accep ed: 16 June 2025
1
Helsinki Ins i u e o Demog aphy and Popula ion Heal h, Uni e si y o Helsinki, Helsinki, Finland.
2
Depa men o Psychology, Uni e si y o Minneso a Twin Ci ies, Minneapolis,
MI, USA.
3
Depa men o Gene ics, Physical An h opology and Animal Physiology, Facul y o Science and Technology, Uni e si y o he Basque Coun y (UPV/EHU), Bilbao, Spain.
4
Ins i u e o Clinical Medicine, Uni e si y o Eas e n Finland, Kuopio, Finland.
5
Ins i u e o Child De elopmen , Uni e si y o Minneso a Twin Ci ies, Minneapolis, MI, USA.
6
Ins i u e
o Molecula Medicine Finland (FIMM), HiLIFE, Uni e si y o Helsinki, Helsinki, Finland. ✉email: ka i.sil en oinen@helsinki.fi
www.na u e.com/p
1234567890();,:
c anio acial measu es
16,17
and high gene ic co ela ions be ween
adiposi y- ela ed measu es.
18
Addi ionally, a s udy o Po uguese
wins e ealed e y high gene ic co ela ions be ween adiposi y-
ela ed measu es.
19
Howe e , hese s udies also ound weake ye
s ill significan gene ic co ela ions o adiposi y- ela ed measu es
wi h heigh
18,19
and c anio acial ai s.
16
Collec i ely, hese s udies
sugges ha while he e a e clus e s o an h opome ic ai s wi h
high gene ic co ela ions, nea ly all body pa s sha e some gene ic
a ia ion.
A limi a ion in p e ious s udies on gene ic co ela ions among
an h opome ic measu es is ha age a ia ion may ha e a ec ed
esul s, as pa ly di e en gene ic ac o s a ec human body pa s
a di e en ages.
11
Fu he mo e, hese s udies lack longi udinal
measu es ha would allow s udying he ole o gene ic ac o s in
g ow h. In his s udy, we will p esen comp ehensi e analyses o
he gene ic backg ound o human body size and mo phology
assessed using 20 an h opome ic measu es, using he win
design. Addi ionally, we will analyze how gene ic ac o s
con ibu e o he g ow h o 15 o hese ai s.
DATA AND METHODS
The s udy coho was de i ed om he Minneso a Twin Family
S udy (MTFS) as desc ibed p e iously.
20
In summa y, he coho
consis ed o same-sex wins bo n in he USA, Minneso a, be ween
1972 and 1984, iden ified h ough Minneso a s a e eco ds.
Con ac in o ma ion was a ailable o 1695 male and 1729 emale
wins, and a ound 80% o hese wins comple ed an in-pe son
in ake assessmen . The wins ep esen ed he Minneso a popula-
ion a he ime, wi h 95% o hem being non-Hispanic whi e and
he majo i y ha ing No he n Eu opean ances y.
The ini ial an h opome ic assessmen was conduc ed when he
child en had a mean age o 11.7 yea s ( anging om 10.7 o 12.8
yea s) and included 1512 win child en (51% gi ls), comp ising 252
male MZ, 233 emale MZ, 124 male DZ, and 147 emale DZ
comple e win pai s. Measu emen s o 15 an h opome ic ai s
we e conduc ed ollowing a specific measu emen p o ocol
(Supplemen a y Table S1): ou measu emen s o body heigh
(heigh , si ing heigh , knee heigh , and bu ock-knee heigh ), he
leng h o bo h ee , fi e measu es o he head (head ci cum e -
ence, head b ead h, ace heigh , and wo measu es o head
leng h), weigh , a m ci cum e ence, and wais ci cum e ence bo h
elaxed and sucking. Addi ionally, we calcula ed body mass index
(BMI) by di iding weigh in kilog ams by he squa e o heigh in
me e s (kg/m
2
). Due o he skewed dis ibu ions o weigh , BMI,
and wais ci cum e ence, we used he loga i hmic ans o ma ion
o no malize hem. Fu he mo e, we adjus ed he ai s o he
exac age sepa a ely o boys and gi ls, as he age e ec was
s a is ically significan o nea ly all measu es (Supplemen a y
Table S2).
The ollow-up assessmen was conduc ed o 624 males wi h an
a e age age o 14.8 yea s old ( anging om 13.6 o 16.9 yea s) and
o 508 emales wi h an a e age age o 18.1 yea s old ( anging
om 16.6 o 20.3 yea s), including 207 male MZ, 161 emale MZ,
104 male DZ and 93 emale DZ comple e pai s. The ollow-up
assessmen included all measu es om he ini ial assessmen , as
well as h ee b ead h measu emen s (shoulde , w is , and hip) and
wo skin old measu es (biceps and iceps) (Supplemen a y
Table S1). Weigh , BMI, wais ci cum e ence, and skin old
measu emen s we e no malized using loga i hmic ans o ma ion
due o skewed dis ibu ions. Nea ly all an h opome ic ai s
showed a s ong age e ec in males bu no in emales because o
hei olde age a he ime o ollow-up assessmen (Supplemen-
a y Table S2). Howe e , o ensu e sys ema ic esul s, we adjus ed
all ai s o age. The age adjus men s we e made by calcula ing
eg ession esiduals using exac age as an independen a iable
sepa a ely in he ini ial and ollow-up assessmen s and in
males and emales. Addi ionally, we conduc ed a ac o analysis
sepa a ely o bo h assessmen s and sexes using he p incipal
ac o es ima o and Va imax o a ion o analyze he unde lying
co ela ion s uc u e. These analyses and all desc ip i e esul s
we e pe o med using S a a/MP 18.0 o Windows.
Twin modeling was used o analyze he ole o gene ic ac o s in
he a ia ion and co- a ia ion o an h opome ic ai s.
21
This
echnique is based on he p inciple ha while MZ wins a e
i ually gene ically iden ical a he gene sequence le el, DZ wins
sha e, on a e age, hal o hei seg ega ing genes, like o dina y
siblings. Since he co ela ion s uc u e be ween co- wins is
known, i is possible o decompose ai a iance in o gene ic
and en i onmen al componen s. Addi i e gene ic a iance (A;
co ela ion 1 wi hin MZ and 0.5 wi hin DZ pai s) includes he
e ec s o all loci influencing he ai . Sha ed en i onmen al
a iance (C; co ela ion 1 wi hin bo h MZ and DZ pai s)
encompasses he e ec s o all en i onmen al ac o s ha make
co- wins simila . Unique en i onmen al a ia ion (E; co ela ion 0
wi hin bo h MZ and DZ wins) includes he e ec s o all
en i onmen al ac o s ha make co- wins dissimila , including
measu emen e o .
Based on co- win co ela ions (Supplemen a y Table S3), we
selec ed he addi i e gene ic/sha ed en i onmen /unique en i -
onmen (ACE) model as ou baseline model. Model fi s a is ics a e
p esen ed in Supplemen a y Table S4. To es he assump ions o
win modeling, we compa ed he ACE model o he sa u a ed
model, which es ima es all possible mean, a iance, and
co a iance s a is ics wi hou assump ions. The ACE models
showed sa is ac o y fi : 11 ai s had poo e fi compa ed o he
sa u a ed model a a con en ional p- alue o 0.05 and ou ai s
(head b ead h, ace heigh , and BMI in he ini ial assessmen and
head b ead h in he ollow-up assessmen s) a a Bon e oni
co ec ed significance le el (p< 0.001 using 37 es s). Sha ed
en i onmen al ac o s we e s a is ically significan o 14 ai s a a
p- alue o 0.05, and o ou ai s a he Bon e oni co ec ed
significance le el (p< 0.001). Gi en ha mos ai s exhibi ed sex
di e ences, we s a ified he models by sex.
Using uni a ia e models, we ini ially calcula ed he p opo ions
o a ia ion explained by addi i e gene ic ac o s (a
2
)–i.e., (na ow
sense) he i abili y es ima es –as well as sha ed en i onmen al (c
2
)
and unique en i onmen al ac o s (e
2
). Subsequen ly, we u ilized
Cholesky decomposi ion, a model- ee me hod o decompose all
a ia ion and co a ia ion in he da a in o unco ela ed la en
ac o s.
22
This me hod was used o decompose he co a ia ion
be ween he an h opome ic measu es in o gene ic and en i on-
men al co a iances. S anda dizing hese co a iances p o ides
es ima es o addi i e gene ic and unique en i onmen al co ela-
ions. Since all ai s showed some e idence o sha ed en i on-
men al a iance, we u ilized he ACE model e en when sha ed
en i onmen al componen s we e no s a is ically significan .
Howe e , in bi a ia e models, we ini ially es ima ed he addi i e
gene ic co ela ions using he AE model and hen confi med hem
using he ACE model. This app oach was used because he sha ed
en i onmen al co ela ions could no be accu a ely calcula ed due
o he small size o sha ed en i onmen al a ia ion. The gene ic
win modeling was conduc ed using he OpenMx package,
e sion 3.0.2, o R s a is ical so wa e. The pa ame e s we e
es ima ed using he linea s uc u al equa ions me hodology and
u ilizing he maximum likelihood es ima o .
23
RESULTS
Table 1p esen s he desc ip i e s a is ics o he an h opome ic
ai s in he ini ial and ollow-up assessmen s. G ow h was
obse ed in all ai s be ween he assessmen s. The ela i e
g ow h was lowes o he head- ela ed ai s (2–3%) and highes
o he adiposi y- ela ed ai s (weigh , BMI, a m ci cum e ence,
and wais ci cum e ence; 15–49%). In he ini ial assessmen , he
measu es we e oughly simila in boys and gi ls. In he ollow-up
K. Sil en oinen e al.
2
Pedia ic Resea ch
assessmen s, he alues a e no compa able due o he age
di e ence.
Table 2p esen s he ela i e a iance componen s o gene ic
and en i onmen al ac o s. Addi i e gene ic ac o s explained a
significan p opo ion o he a ia ion in all an h opome ic ai s,
wi h he i abili y es ima es gene ally lowe o c anio acial ai s (a
2
anged be ween 0.21 and 0.85) compa ed o he o he ai s (a
2
anged be ween 0.23 and 0.90). Sha ed en i onmen al ac o s also
con ibu ed o he a ia ion in mos ai s (c
2
anged be ween 0.00
and 0.63), al hough he sha ed en i onmen al a iances we e no
s a is ically significan o many ai s. The e we e no consis en
di e ences in he he i abili y es ima es be ween males and
emales. In gene al, sha ed en i onmen al ac o s explained mo e
and addi i e gene ic ac o s less o he ai a ia ion in he ollow-
up han in he ini ial assessmen .
A e comple ing he uni a ia e analyses, we p oceeded o
analyze he mu ual co ela ions be ween he ai s in he ini ial
assessmen . Fac o analysis e ealed h ee ac o s in bo h males
and emales: he fi s ac o eflec ed linea ai s (heigh - ela ed
ai s and oo -leng h), he second ac o eflec ed olume ai s
(BMI, a m ci cum e ence, and wais ci cum e ence), and he hi d
ac o eflec ed c anio acial ai s ( he ac o analyses a ailable in
Supplemen a y Table S5, he ai co ela ions in Supplemen a y
Fig. S1, and hei 95% CIs in Supplemen a y Table S6). Howe e ,
all ai s showed some loading on all h ee ac o s. Nex , we
decomposed he ai co ela ions in o gene ic and unique
en i onmen al co ela ions. Figu e 1p esen s he addi i e gene ic
co ela ions o boys (uppe diagonal ma ix) and gi ls (lowe
diagonal ma ix) (95% CIs a e a ailable in Supplemen a y Table S7).
Two clus e s o gene ic co ela ions we e iden ified: he compo-
nen s o heigh and oo leng h exhibi ed high gene ic co ela-
ions (
A
=0.69–1.00), as did he adiposi y- ela ed ai s
(
A
=0.85–0.98). Howe e , mos o he gene ic co ela ions we e
mode a e (
A
≥0.30) indica ing ha all ai s sha ed some gene ic
a ia ion. Since hese co ela ions may be influenced by sha ed
en i onmen al ac o s, we ecalcula ed hem allowing sha ed
en i onmen al co ela ions (Supplemen a y Table S8). Howe e ,
he changes we e gene ally modes , and, in some cases, he
co ela ions inc eased. Sha ed en i onmen al co ela ions could
no be eliably es ima ed, and 95% CIs we e e y b oad, anging
o many ai pai s om −1.00 o 1.00 (Supplemen a y Table S9).
We also iden ified he unique en i onmen al co ela ions be ween
he ai s, bu hey we e lowe han he addi i e gene ic
co ela ions (Supplemen a y Fig. S2; 95% confidence in e als
a e p esen ed in Supplemen a y Table S10).
We epea ed he analyses using he mo e comp ehensi e
an h opome ic measu emen s a ailable in he ollow-up assess-
men . Gene ally, he esul s aligned wi h hose om he ini ial
assessmen . In he ac o analysis, we iden ified h ee ac o s in
bo h males and emales: he fi s ac o eflec ed olume ai s, he
second ac o eflec ed linea ai s, and he hi d ac o eflec ed
c anio acial ai s ( he ac o analysis is a ailable in Supplemen a y
Table S11, he ai co ela ion in Supplemen a y Fig. S3, and hei
95% CIs in Supplemen a y Table S12). Figu e 2p esen s he
addi i e gene ic co ela ions o boys (uppe diagonal ma ix) and
gi ls (lowe diagonal ma ix) (95% CIs a e p esen ed in Supple-
men a y Table S13). We obse ed clus e s o gene ic co ela ions
wi hin he heigh - ela ed ai s and oo -leng h (
A
=0.58–1.00)
and adiposi y- ela ed ai s (
A
=0.70–0.96). Howe e , skin old
hicknesses exhibi ed only mode a e gene ic co ela ions wi h he
adiposi y- ela ed ai s (
A
=0.26–0.50), and he co ela ions wi h
o he ai s we e close o ze o. C anio acial ai s showed
somewha weake mu ual co ela ions (
A
=0.26–0.80), and hey
also had mode a e gene ic co ela ions (
A
≥0.30) wi h heigh -
Table 1. Desc ip i e s a is ics o age and an h opome ic ai s in he ini ial and ollow-up assessmen s by sex.
Ini ial assessmen Follow-up assessmen
Male Female Male Female
mean SD mean SD mean SD mean SD
Age yea s 11.7 0.39 11.7 0.46 14.8 0.49 18.3 0.71
Heigh cm 149 7.02 151 7.31 170 7.85 166 6.4
Si ing heigh cm 77.1 3.48 78.2 4.12 86.8 4.47 87.1 3.25
Knee heigh cm 46.7 2.84 46.8 2.77 52.9 2.85 50.5 2.63
Bu ock-knee leng h cm 51.7 3.23 52.7 3.44 59.1 3.34 58.4 2.94
Foo leng h le cm 23.0 1.42 22.5 1.31 25.7 1.38 23.5 1.25
Foo leng h igh cm 23.1 1.38 22.5 1.32 25.7 1.37 23.6 1.25
Head ci cum e ence cm 54.1 1.62 54.1 1.75 55.9 1.68 55.5 1.75
Head b ead h cm 14.4 0.48 14.3 0.50 14.9 0.53 14.6 0.52
Face heigh cm 20.7 1.09 20.0 1.12 21.8 1.07 20.8 1.03
Head leng h 1 cm 18.6 0.70 18.3 0.81 19.0 0.84 18.8 0.82
Head leng h 2 cm 16.8 0.86 16.4 0.95 17.3 0.95 17.2 0.84
Weigh kg 41.3 9.53 44.5 11.26 61.7 13.03 65.2 14.73
BMI kg/m
2
18.4 3.22 19.4 3.73 21.2 3.58 23.7 4.91
A m ci cum e ence cm 21.8 2.88 22.6 3.24 25.9 3.29 26.6 3.67
Wais ci c. elaxed cm 65.7 9.00 67.2 9.74 76.2 9.17 78.5 11.28
Wais ci c. sucking cm 60.6 8.87 62.6 9.90 71.1 9.69 73.2 11.31
Shoulde b ead h cm NA NA NA NA 33.8 3.07 34.2 2.88
W is b ead h cm NA NA NA NA 5.56 0.33 5.18 0.33
Hip b ead h cm NA NA NA NA 30.4 3.03 34.3 3.17
Biceps skin old mm NA NA NA NA 8.19 5.93 11.73 6.71
T iceps skin old mm NA NA NA NA 13.3 8.30 20.1 7.89
K. Sil en oinen e al.
3
Pedia ic Resea ch
Table 2. Rela i e a iance componen s o addi i e gene ic, sha ed en i onmen al, and unique en i onmen al ac o s o an h opome ic ai s by sex.
Males Females
Addi i e gene ic
ac o s
Sha ed en i onmen al
ac o s
Unique en i onmen al
ac o s
Addi i e gene ic
ac o s
Sha ed en i onmen al
ac o s
Unique en i onmen al
ac o s
a
2
95% CI c
2
95% CI e
2
95% CI a
2
95% CI c
2
95% CI e
2
95% CI
LL UL LL UL LL UL LL UL LL UL LL UL
Ini ial assessmen
Heigh 0.78 0.57 0.94 0.15 0.00 0.36 0.07 0.06 0.09 0.71 0.54 0.93 0.22 0.00 0.40 0.07 0.05 0.08
Si ing heigh 0.75 0.52 0.88 0.11 0.00 0.34 0.14 0.11 0.17 0.67 0.49 0.90 0.23 0.00 0.42 0.10 0.08 0.12
Knee heigh 0.81 0.60 0.94 0.11 0.00 0.32 0.07 0.06 0.09 0.73 0.53 0.91 0.17 0.00 0.37 0.10 0.08 0.12
Bu ock-knee leng h 0.39 0.22 0.61 0.44 0.22 0.60 0.17 0.14 0.21 0.73 0.53 0.89 0.14 0.00 0.34 0.13 0.10 0.16
Foo leng h le 0.82 0.60 0.92 0.08 0.00 0.30 0.09 0.08 0.12 0.66 0.47 0.89 0.23 0.00 0.42 0.11 0.09 0.14
Foo leng h igh 0.83 0.61 0.93 0.09 0.00 0.31 0.08 0.07 0.10 0.64 0.45 0.88 0.23 0.00 0.42 0.13 0.10 0.16
Head ci c 0.49 0.30 0.74 0.35 0.09 0.53 0.17 0.14 0.21 0.84 0.61 0.88 0.01 0.00 0.24 0.15 0.12 0.18
Head b ead h 0.73 0.49 0.84 0.08 0.00 0.31 0.20 0.16 0.24 0.73 0.53 0.89 0.14 0.00 0.33 0.13 0.11 0.17
Head leng h 1 0.58 0.34 0.80 0.19 0.00 0.41 0.24 0.19 0.29 0.67 0.43 0.81 0.11 0.00 0.34 0.23 0.18 0.28
Head leng h 2 0.53 0.31 0.81 0.26 0.00 0.48 0.21 0.17 0.25 0.48 0.29 0.71 0.34 0.12 0.52 0.18 0.15 0.23
Face heigh 0.30 0.07 0.62 0.37 0.03 0.61 0.34 0.28 0.40 0.41 0.10 0.65 0.17 0.00 0.45 0.42 0.35 0.50
Weigh 0.79 0.59 0.92 0.12 0.00 0.32 0.09 0.07 0.11 0.78 0.59 0.93 0.14 0.00 0.33 0.08 0.06 0.10
BMI 0.79 0.59 0.92 0.12 0.00 0.32 0.09 0.07 0.11 0.82 0.63 0.93 0.10 0.00 0.29 0.08 0.07 0.10
A m ci c 0.76 0.55 0.90 0.11 0.00 0.32 0.12 0.10 0.15 0.83 0.62 0.92 0.07 0.00 0.28 0.10 0.08 0.12
Wais ci c. elax 0.55 0.36 0.78 0.30 0.07 0.48 0.15 0.12 0.19 0.65 0.45 0.86 0.19 0.00 0.39 0.15 0.12 0.19
Wais ci c. sucking 0.68 0.47 0.87 0.17 0.00 0.38 0.15 0.12 0.19 0.68 0.48 0.88 0.18 0.00 0.38 0.14 0.11 0.17
Follow-up assessmen
Heigh 0.65 0.44 0.90 0.24 0.00 0.46 0.11 0.09 0.14 0.78 0.54 0.95 0.17 0.00 0.41 0.06 0.04 0.07
Si ing heigh 0.67 0.44 0.88 0.18 0.00 0.41 0.15 0.12 0.19 0.87 0.83 0.90 0.00 0.00 0.19 0.13 0.10 0.17
Knee heigh 0.62 0.41 0.88 0.24 0.00 0.45 0.13 0.11 0.17 0.70 0.41 0.85 0.11 0.00 0.39 0.19 0.15 0.25
Bu ock-knee leng h 0.46 0.26 0.71 0.37 0.12 0.56 0.17 0.14 0.22 0.63 0.35 0.84 0.18 0.00 0.45 0.19 0.15 0.25
Foo leng h le 0.69 0.45 0.86 0.14 0.00 0.38 0.17 0.13 0.21 0.90 0.87 0.92 0.00 0.00 0.19 0.10 0.08 0.13
Foo leng h igh 0.67 0.44 0.87 0.17 0.00 0.40 0.16 0.13 0.20 0.88 0.85 0.91 0.00 0.00 0.27 0.12 0.09 0.15
Head ci c 0.57 0.35 0.84 0.25 0.00 0.47 0.18 0.14 0.22 0.85 0.80 0.88 0.00 0.00 0.27 0.15 0.12 0.20
Head b ead h 0.67 0.44 0.85 0.15 0.00 0.38 0.18 0.14 0.22 0.84 0.79 0.88 0.00 0.00 0.24 0.16 0.12 0.21
Head leng h 1 0.43 0.21 0.72 0.35 0.06 0.56 0.22 0.18 0.27 0.44 0.13 0.73 0.23 0.00 0.50 0.33 0.26 0.42
Head leng h 2 0.37 0.17 0.63 0.43 0.17 0.62 0.20 0.16 0.25 0.54 0.22 0.73 0.12 0.00 0.41 0.34 0.27 0.43
Face heigh 0.21 0.00 0.53 0.42 0.11 0.64 0.37 0.30 0.46 0.65 0.29 0.73 0.01 0.00 0.35 0.34 0.27 0.43
Shoulde b ead h 0.27 0.10 0.48 0.55 0.34 0.70 0.19 0.15 0.24 0.23 0.09 0.41 0.63 0.45 0.77 0.14 0.11 0.18
W is b ead h 0.64 0.38 0.82 0.14 0.00 0.38 0.22 0.18 0.28 0.61 0.31 0.82 0.17 0.00 0.46 0.22 0.17 0.28
Weigh 0.71 0.50 0.91 0.19 0.00 0.40 0.10 0.08 0.12 0.71 0.47 0.91 0.18 0.00 0.42 0.11 0.09 0.15
BMI 0.77 0.55 0.91 0.12 0.00 0.34 0.11 0.09 0.14 0.62 0.40 0.89 0.26 0.00 0.48 0.12 0.09 0.16
A m ci c 0.79 0.56 0.91 0.10 0.00 0.33 0.12 0.09 0.15 0.67 0.39 0.83 0.11 0.00 0.38 0.22 0.17 0.29
K. Sil en oinen e al.
4
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ela ed and adiposi y- ela ed ai s. When we es ima ed he
addi i e gene ic co ela ions while allowing o sha ed en i on-
men al co ela ions, he changes we e gene ally modes and in
some cases he co ela ions inc eased (Supplemen a y Table S14).
In alignmen wi h he ini ial assessmen , he sha ed en i onmen al
co ela ions could no be eliably es ima ed (Supplemen a y
Table S15). Unique en i onmen al co ela ions we e lowe han
addi i e gene ic co ela ions (Supplemen a y Fig. S4; 95%
confidence in e als a e p esen ed in Supplemen a y Table S16).
Finally, we examined he co ela ions o an h opome ic ai s
be ween he ini ial and ollow-up assessmen s (Table 3). The ai
co ela ions anged om 0.34 o 0.90. Co ela ions o ace heigh
and leng h we e lowe han o o he ai s, bu no sys ema ic
di e ences we e obse ed o he wise. Addi i e gene ic co ela-
ions we e consis en ly highe , while unique en i onmen al
co ela ions we e lowe han he ai co ela ions.
DISCUSSION
In his comp ehensi e s udy o human body size and mo phology,
we obse ed ha gene ic ac o s explained a majo p opo ion o
he a ia ion in 21 an h opome ic ai s. Fo heigh and BMI, he
he i abili y es ima es we e high, showing ha be ween 62% o 82%
o he a ia ion is explained by gene ic di e ences. Howe e , sha ed
en i onmen al ac o s also explained a po ion o he a ia ion in
nea ly all an h opome ic ai s. The e was also some e idence ha
he p opo ion o sha ed en i onmen al a ia ion inc eased om
he ini ial o he ollow-up assessmen . This esul is di e en han
wha was ound in la ge-scale win s udies on heigh
3
and BMI,
5
sugges ing ha sha ed en i onmen al a ia ion ends o dec ease
om childhood o adolescence. Howe e , he e is a lack o s udies
on o he an h opome ic measu es a di e en ages, and he CIs o
sha ed en i onmen al a iance in ou s udy we e wide. Di e en ia -
ing be ween sha ed en i onmen al ac o s and gene ic ac o s
equi es conside able s a is ical powe ,
24
o en leading o he
neglec o sha ed en i onmen al ac o s in gene ic win s udies.
These esul s sugges ha sha ed en i onmen al ac o s can a ec
he a ia ion o an h opome ic ai s along wi h gene ic ac o s and
should be be e ecognized in u u e s udies. In e es ingly, he
he i abili y es ima es o c anio acial ai s we e consis en ly lowe
compa ed o heigh - and adiposi y- ela ed ai s, sugges ing ha
en i onmen al ac o s unique o indi iduals may play a ole in
shaping acial ea u es. P e ious s udies using pedig ee da a ha e
epo ed he i abili y es ima es o c anio acial measu es a a
simila le el o hose in ou s udy.
16,25
Howe e , measu emen
e o is also included in unique en i onmen al a ia ion, which
can explain he lowe he i abili y o hese ai s.
Fo 16 o hese 21 ai s, we had longi udinal measu es ha
allowed us o examine ac o s ela ed o g ow h o e adolescence,
om abou 11 yea s onwa d. As expec ed, he e was subs an ial
g ow h o heigh - and adiposi y- ela ed ai s, bu minimal
g ow h o c anio acial ai s, eflec ing he no mal physical
de elopmen o child en du ing adolescence.
26
Gene ic co ela-
ions o heigh - and adiposi y- ela ed ai s we e high, indica ing
ha a la ge p opo ion o he gene ic ac o s a ec ing hese ai s
du ing pube y a e he same. These gene ic co ela ions we e e y
simila o hose ound o heigh and BMI du ing adolescence in a
p e ious la ge-scale win s udy ha pooled da a om se e al win
coho s.
11
Fo c anio acial ai s, he gene ic co ela ions we e
lowe han o o he ai s, sugges ing ha pa ly di e en se s o
gene ic ac o s begin o shape he head du ing adolescence.
These esul s indica e ha he gene ic egula ion o di e en pa s
o he body can a y o e he cou se o aging. Howe e , i is
no ewo hy ha he e can be mo e measu emen e o in
c anio acial han in o he measu emen s, which can also lead o
lowe gene ic co ela ions.
We iden ified h ee clus e s o gene ic co ela ions. Fi s ly,
heigh - ela ed measu es and he leng h o bo h ee exhibi ed
Table 2. con inued
Males Females
Addi i e gene ic
ac o s
Sha ed en i onmen al
ac o s
Unique en i onmen al
ac o s
Addi i e gene ic
ac o s
Sha ed en i onmen al
ac o s
Unique en i onmen al
ac o s
a
2
95% CI c
2
95% CI e
2
95% CI a
2
95% CI c
2
95% CI e
2
95% CI
LL UL LL UL LL UL LL UL LL UL LL UL
Hip b ead h 0.59 0.40 0.84 0.31 0.06 0.50 0.11 0.08 0.13 0.48 0.27 0.78 0.36 0.07 0.57 0.16 0.12 0.21
Wais ci c. elax 0.61 0.39 0.85 0.22 0.00 0.44 0.18 0.14 0.22 0.83 0.78 0.87 0.00 0.00 0.27 0.17 0.13 0.22
Wais ci c. sucking 0.49 0.27 0.77 0.31 0.06 0.52 0.20 0.16 0.26 0.45 0.21 0.77 0.35 0.03 0.58 0.20 0.16 0.26
Biceps skin old 0.57 0.36 0.84 0.26 0.00 0.46 0.17 0.13 0.21 0.15 0.00 0.41 0.60 0.35 0.76 0.25 0.19 0.32
T iceps skin old 0.42 0.23 0.67 0.40 0.16 0.58 0.18 0.14 0.22 0.24 0.00 0.54 0.47 0.19 0.68 0.30 0.23 0.38
K. Sil en oinen e al.
5
Pedia ic Resea ch
high gene ic co ela ions. La ge GWA s udies
27
and whole-
genome s udies
28
ha e iden ified nume ous genes associa ed
wi h heigh . Genes con ibu ing o skele al g ow h and he
de elopmen o ca ilage and connec i e issues a e en iched in
hese s udies. Building on such gene ic findings, s udies using
immo alized chond ogenic mu ine cell lines demons a ed ha
genes associa ed wi h heigh a e exp essed highly in g ow h pla e
chond ocy es.
27,29
Ou findings sugges ha pa ly he same
gene ic ac o s egula e he ossifica ion o long bones and ee
bones. The second clus e encompassed adiposi y- ela ed ai s,
which ha e also shown high gene ic co ela ions in p e ious
pedig ee
18
and win s udies.
19
E idence om GWA, win, and
epidemiological s udies suppo s he idea ha ea ing beha io
plays a significan ole in media ing he influences o gene ic
ac o s on BMI.
30
The e o e, nu i ion p obably influences hese
gene ic co ela ions. Howe e , unlike p e ious s udies,
18,19
ou
s udy ound only mode a e gene ic co ela ions be ween skin old
hicknesses and BMI/wais ci cum e ence. A p e ious GWA s udy
indica ed ha gene ic a ian s linked o body a dis ibu ion a e
associa ed wi h lipid me abolism and adipose issue egula ion.
31
I is possible ha hese gene ic e ec s a e mo e p onounced in
adolescence, leading o dec eased gene ic co ela ions in ou
da a. The hi d clus e in ol ed c anio acial ai s, bu he gene ic
co ela ions among hem we e weake compa ed o heigh - and
adiposi y- ela ed ai s. The gene ic complexi y o c anio acial
ai s was also highligh ed in a ecen GWA s udy.
32
These esul s
a e expec ed gi en he in ica e na u e o he head, which
comp ises bo h so and bone issues likely influenced by dis inc
gene ic ac o s.
In addi ion o hese clus e s o gene ic co ela ions, we ound
ha nea ly all ai s showed some sha ed gene ic a ia ion, as
seen in p e ious s udies. The gene ic co ela ions we e gene ally
highe han he ai co ela ions, indica ing ha mainly gene ic
ac o s a e behind he an h opome ic co ela ions. These esul s
a e no su p ising, as pleio opy is e y common in human ai s.
33
Howe e , he e can be se e al mechanisms behind pleio opic
e ec s,
34
and we can only specula e on which ac o s explain
hem in ou s udy. Since all body pa s a e o med by he same
issues, he unde lying sha ed gene ic mechanisms ha egula e
he g ow h and de elopmen o bone, adipose, and muscle issues
can explain gene ic co ela ions be ween e en dis inc body pa s
such as c anio acial and adiposi y- ela ed ai s. These gene ic
co ela ions may ha e a backg ound in emb yonic de elopmen
when di e en body pa s de elop om he same emb yonic
s uc u es.
35
I is also possible ha he pos na al en i onmen ,
especially nu i ion, can a ec di e en ai s and explain hese
gene ic co ela ions.
30
This is e iden o adiposi y- ela ed ai s
bu may also explain co ela ions be ween heigh - and adiposi y-
ela ed ai s. Disen angling hese di e en mechanisms equi es
di e en s udy designs, such as combining de ailed measu es o
po en ial en i onmen al ac o s wi h longi udinal an h opome ic
measu es.
Since we ound e idence o sha ed en i onmen al ac o s,
we also s udied he sha ed en i onmen al co ela ions be ween
0.44 0.45 0.42 0.66 0.45 0.46 0.54 0.39 0.32 0.45 0.47 0.85 0.87 0.85 0.98
0.44 0.46 0.43 0.65 0.45 0.47 0.53 0.37 0.29 0.42 0.49 0.88 0.90 0.87 0.98
0.43 0.52 0.40 0.65 0.43 0.46 0.55 0.40 0.34 0.46 0.42 0.91 0.94 0.88 0.87
0.37 0.47 0.35 0.61 0.39 0.42 0.52 0.41 0.28 0.41 0.42 0.93 0.91 0.90 0.89
0.68 0.72 0.64 0.82 0.61 0.65 0.62 0.44 0.36 0.48 0.54 0.91 0.90 0.92 0.91
0.52 0.56 0.43 0.50 0.57 0.54 0.59 0.33 0.46 0.46 0.47 0.33 0.39 0.38 0.39
0.40 0.45 0.32 0.45 0.39 0.42 0.59 0.36 0.79 0.44 0.53 0.43 0.42 0.48 0.50
0.35 0.34 0.27 0.40 0.36 0.36 0.70 0.40 0.69 0.39 0.39 0.31 0.32 0.32 0.32
0.31 0.34 0.22 0.37 0.29 0.29 0.71 0.26 0.27 0.30 0.38 0.33 0.36 0.34 0.34
0.53 0.55 0.43 0.59 0.49 0.50 0.58 0.72 0.60 0.48 0.52 0.44 0.45 0.48 0.47
0.80 0.71 0.79 0.76 1.00 0.41 0.30 0.38 0.47 0.42 0.68 0.40 0.47 0.54 0.53
0.77 0.66 0.78 0.76 0.99 0.39 0.29 0.35 0.44 0.39 0.68 0.40 0.48 0.54 0.53
0.86 0.72 0.86 0.76 0.78 0.44 0.32 0.35 0.52 0.47 0.78 0.51 0.60 0.69 0.68
0.92 0.71 0.85 0.79 0.80 0.38 0.28 0.32 0.40 0.44 0.63 0.30 0.43 0.48 0.50
0.89 0.71 0.69 0.75 0.77 0.44 0.32 0.34 0.45 0.51 0.72 0.43 0.53 0.53 0.51
0.88 0.91 0.87 0.83 0.85 0.42 0.28 0.34 0.46 0.48 0.67 0.30 0.45 0.50 0.51
wais _C_suck
wais _C_ elax
a m_C
BMI
weigh
ace_H
head_L_2
head_L_1
head_B
head_C
oo _L_ igh
oo _L_le
bu ock_knee_L
knee_H
si ing_H
o al_H
o al_H
si ing_H
knee_H
bu ock_knee_L
oo _L_le
oo _L_ igh
head_C
head_B
head_L_1
head_L_2
ace_H
weigh
BMI
a m_C
wais _C_ elax
wais _C_suck
T ai
T ai
–1.0
–0.5
0.0
0.5
1.0
Co
Fig. 1 Addi i e gene ic co ela ions o an h opome ic ai s in males (uppe diagonal ma ix) and emales (lowe diagonal ma ix) in he
ini ial assessmen . B b ead h, C ci cum e ence, H heigh , L leng h.
K. Sil en oinen e al.
6
Pedia ic Resea ch
he ai s. Howe e , we ound ha he sha ed en i onmen al
a iance componen s we e oo low o eliably es ima e hese
co ela ions. The e o e, we canno de e mine i he e a e
en i onmen al ac o s sha ed by co- wins ha a ec di e en
an h opome ic ai s. We calcula ed all gene ic co ela ions while
also accoun ing o sha ed en i onmen al influences, bu his had
a modes e ec on he magni ude o gene ic co ela ions, and in
some cases, hey e en inc eased. This suppo s he conclusion
ha he gene ic co ela ions eflec a sha ed gene ic backg ound
be ween he ai s a he han unspecified amilial e ec s
combining sha ed gene ic and en i onmen al influences.
Ou s udy has s eng hs and limi a ions. We ha e de ailed
an h opome ic measu emen s in gene ically in o ma i e da a
allowing us o analyze he gene ics o body mo phology in de ail.
Addi ionally, we had longi udinal da a o se e al ai s, which
enabled us o analyze how gene ic ac o s impac g ow h du ing
adolescence. Ou da ase was no la ge enough o simul aneously
es ima e gene ic and sha ed en i onmen al e ec s wi h su ficien
powe . Howe e , we confi med ha sha ed en i onmen al ac o s
had minimal impac on gene ic co ela ions. Ou main limi a ion is
he lack o dual-ene gy X- ay abso p iome y (DEXA) o compu e
omog aphy measu emen s, which would ha e allowed us o
di ec ly measu e body composi ion. Likewise, magne ic esonance
imaging (MRI) could be used o assess, o example, he bony
s uc u e o he skull. This in o ma ion would ha e been aluable in
analyzing he ex en o which di e en an h opome ic ai s sha e
common gene ic a iance wi h body composi ion measu es. The
popula ion o Minneso a du ing he da a collec ion pe iod was
e hnically homogeneous. I is likely ha in mo e he e ogeneous
popula ions, he i abili y es ima es would be lowe compa ed o his
s udy, due o a la ge sha ed en i onmen al a ia ion.
In conclusion, we ound ha sha ed gene ic ac o s b oadly
a ec he body size and mo phology o humans. Clus e s o high
gene ic co ela ions we e iden ified o heigh - and adiposi y-
ela ed ai s, bu mos o he ai s sha ed some gene ic a ia ion.
Gene ic ac o s also la gely explained he co ela ions o hese
ai s o e adolescence. Pleio opic e ec s a e impo an o
unde s anding he gene ic egula ion o human physique.
0.03 0.13 0.10 0.14 0.12 0.13 0.08 0.14 0.02 0.04 0.09 0.06 0.07 0.35 0.39 0.40 0.31 0.36 0.34 0.75
−0.01 0.10 0.03 0.13 0.07 0.08 0.12 0.12 0.05 0.14 0.09 0.09 0.06 0.35 0.40 0.36 0.20 0.38 0.31 0.85
0.18 0.22 0.28 0.55 0.33 0.31 0.41 0.31 0.23 0.32 0.26 0.35 0.48 0.89 0.89 0.90 0.78 0.96 0.51 0.49
0.21 0.24 0.31 0.54 0.36 0.34 0.40 0.28 0.29 0.33 0.27 0.34 0.48 0.88 0.87 0.86 0.74 0.97 0.52 0.49
0.30 0.40 0.39 0.60 0.42 0.40 0.36 0.34 0.28 0.34 0.20 0.38 0.44 0.87 0.83 0.81 0.71 0.69 0.48 0.46
0.18 0.26 0.28 0.55 0.29 0.28 0.40 0.33 0.30 0.34 0.23 0.30 0.48 0.90 0.93 0.67 0.82 0.81 0.48 0.49
0.05 0.19 0.18 0.45 0.24 0.23 0.38 0.34 0.27 0.35 0.17 0.40 0.49 0.92 0.93 0.70 0.88 0.85 0.50 0.50
0.43 0.50 0.51 0.71 0.52 0.51 0.48 0.34 0.35 0.46 0.32 0.46 0.61 0.90 0.89 0.77 0.87 0.86 0.43 0.45
0.43 0.43 0.41 0.52 0.49 0.50 0.31 0.28 0.20 0.36 0.27 0.21 0.59 0.43 0.53 0.56 0.38 0.42 0.12 0.14
0.26 0.28 0.39 0.24 0.32 0.33 0.29 0.15 0.08 0.28 0.24 0.49 0.51 0.36 0.41 0.47 0.31 0.35 0.08 0.15
0.43 0.48 0.41 0.38 0.42 0.42 0.49 0.26 0.45 0.43 0.41 0.45 0.63 0.47 0.54 0.48 0.45 0.51 0.19 0.21
0.39 0.48 0.36 0.33 0.39 0.36 0.61 0.33 0.72 0.60 0.37 0.41 0.57 0.47 0.49 0.33 0.42 0.46 0.18 0.23
0.29 0.31 0.26 0.33 0.32 0.27 0.69 0.28 0.80 0.51 0.28 0.30 0.38 0.31 0.32 0.19 0.25 0.27 0.04 0.10
0.09 0.19 0.10 0.12 0.16 0.17 0.60 0.32 0.33 0.45 0.23 0.32 0.44 0.37 0.39 0.29 0.30 0.35 0.09 0.13
0.34 0.43 0.33 0.34 0.39 0.39 0.65 0.75 0.65 0.59 0.40 0.41 0.58 0.47 0.48 0.44 0.47 0.49 0.14 0.17
0.77 0.69 0.78 0.69 1.00 0.42 0.30 0.33 0.44 0.54 0.47 0.65 0.62 0.32 0.37 0.50 0.42 0.44 0.08 0.10
0.76 0.69 0.78 0.69 0.99 0.44 0.29 0.33 0.41 0.51 0.45 0.63 0.62 0.33 0.39 0.48 0.43 0.44 0.06 0.08
0.78 0.58 0.81 0.72 0.70 0.50 0.28 0.35 0.47 0.57 0.45 0.50 0.70 0.40 0.46 0.53 0.57 0.59 0.20 0.25
0.90 0.70 0.86 0.76 0.78 0.38 0.23 0.26 0.37 0.45 0.43 0.47 0.56 0.20 0.27 0.40 0.37 0.39 0.04 0.09
0.84 0.61 0.63 0.64 0.66 0.50 0.39 0.35 0.53 0.61 0.57 0.56 0.70 0.39 0.49 0.53 0.40 0.44 0.08 0.13
0.85 0.89 0.86 0.78 0.79 0.47 0.32 0.30 0.42 0.56 0.50 0.56 0.63 0.24 0.34 0.48 0.39 0.42 0.08 0.12
iceps_SF
biceps_SF
wais _C_suck
wais _C_ elax
hip_B
a m_C
BMI
weigh
w is _B
shoulde _B
ace_H
head_L_2
head_L_1
head_B
head_C
oo _L_ igh
oo _L_le
bu ock_knee_L
knee_H
si ing_H
o al_H
o al_H
si ing_H
knee_H
bu ock_knee_L
oo _L_le
oo _L_ igh
head_C
head_B
head_L_1
head_L_2
ace_H
shoulde _B
w is _B
weigh
BMI
a m_C
hip_B
wais _C_ elax
wais _C_suck
biceps_SF
iceps_SF
T ai
T ai
–1.0
–0.5
0.0
0.5
1.0
Co
Fig. 2 Addi i e gene ic co ela ions o an h opome ic ai s in males (uppe diagonal ma ix) and emales (lowe diagonal ma ix) in he
ollow-up assessmen s. B b ead h, C ci cum e ence, H heigh , L leng h, SF skin old.
K. Sil en oinen e al.
7
Pedia ic Resea ch
DATA AVAILABILITY
The da a a e eely a ailable o esea ch pu poses. Any inqui ies should be sen o
Ma McGue ([email p o ec ed]).
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Table 3. T ai co ela ions and addi i e gene ic and unique en i onmen al co ela ions be ween he an h opome ic ai s in ini ial and ollow-up
assessmen s by sex.
T ai co ela ion Addi i e gene ic co ela ion Unique en i onmen al
co ela ion
95% CI
A
95% CI
E
95% CI
LL
UL LL UL LL UL
Males
Heigh 0.87 0.85 0.89 0.90 0.87 0.92 0.56 0.46 0.64
Si ing heigh 0.79 0.76 0.82 0.85 0.81 0.88 0.41 0.29 0.51
Knee heigh 0.80 0.77 0.83 0.85 0.82 0.88 0.37 0.26 0.48
Bu ock-knee leng h 0.79 0.76 0.82 0.86 0.82 0.9 0.36 0.24 0.47
Foo leng h le 0.81 0.78 0.84 0.87 0.83 0.9 0.41 0.29 0.51
Foo leng h igh 0.82 0.79 0.84 0.88 0.85 0.91 0.35 0.23 0.46
Head ci cum e ence 0.75 0.71 0.78 0.79 0.74 0.83 0.60 0.51 0.67
Head b ead h 0.87 0.85 0.89 0.93 0.91 0.95 0.60 0.52 0.68
Face heigh 0.48 0.41 0.54 0.64 0.54 0.73 0.12 0.00 0.24
Head leng h 1 0.65 0.60 0.69 0.75 0.69 0.81 0.30 0.18 0.42
Head leng h 2 0.45 0.38 0.51 0.49 0.39 0.57 0.27 0.15 0.39
Weigh 0.91 0.90 0.92 0.94 0.92 0.95 0.64 0.56 0.71
BMI 0.90 0.89 0.92 0.95 0.93 0.96 0.53 0.43 0.62
A m ci cum e ence 0.82 0.79 0.84 0.86 0.82 0.89 0.52 0.42 0.61
Wais ci c. elaxed 0.80 0.77 0.83 0.88 0.85 0.91 0.41 0.30 0.51
Wais ci c. sucking 0.75 0.72 0.79 0.84 0.79 0.88 0.37 0.25 0.48
Females
Heigh 0.71 0.66 0.75 0.73 0.67 0.78 0.49 0.36 0.59
Si ing heigh 0.68 0.63 0.73 0.73 0.67 0.79 0.29 0.15 0.43
Knee heigh 0.70 0.65 0.74 0.78 0.72 0.83 0.13 -0.02 0.28
Bu ock-knee leng h 0.66 0.61 0.71 0.72 0.64 0.78 0.34 0.20 0.47
Foo leng h le 0.82 0.79 0.84 0.83 0.79 0.87 0.62 0.51 0.71
Foo leng h igh 0.81 0.78 0.84 0.85 0.81 0.89 0.46 0.33 0.57
Head ci cum e ence 0.72 0.67 0.76 0.77 0.70 0.82 0.40 0.26 0.52
Head b ead h 0.83 0.80 0.85 0.87 0.83 0.90 0.61 0.50 0.70
Face heigh 0.49 0.42 0.56 0.70 0.59 0.81 0.06 -0.09 0.21
Head leng h 1 0.51 0.44 0.57 0.59 0.48 0.68 0.29 0.15 0.42
Head leng h 2 0.34 0.26 0.42 0.40 0.27 0.51 0.23 0.08 0.37
Weigh 0.78 0.74 0.81 0.80 0.75 0.84 0.52 0.39 0.62
BMI 0.79 0.76 0.82 0.82 0.78 0.86 0.43 0.29 0.54
A m ci cum e ence 0.70 0.65 0.74 0.77 0.70 0.83 0.3 0.15 0.43
Wais ci c. elaxed 0.66 0.60 0.70 0.72 0.64 0.78 0.22 0.06 0.36
Wais ci c. sucking 0.62 0.56 0.67 0.68 0.59 0.75 0.28 0.14 0.42
K. Sil en oinen e al.
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ACKNOWLEDGEMENTS
KS and JK a e wo king in he BETTER4U p ojec . The BETTER4U p ojec has ecei ed unding
om he Eu opean Union’s Ho izon Eu ope Resea ch and Inno a ion p og am unde G an
Ag eemen #101080117, by UK Resea ch and Inno a ion (UKRI) unde he UK go e nmen ’s
Ho izon Eu ope unding gua an ee (g an #10093560 o Queen Ma y Uni e si y o London
and #10106435 o Bo n in B ad o d) and om he Swiss S a e Sec e a ia o Educa ion,
Resea ch and Inno a ion (SERI). Views and opinions exp essed a e, howe e , hose o he
au ho (s) only and do no necessa ily eflec hose o he Eu opean Union.
AUTHOR CONTRIBUTIONS
K.S., R.F.K. and M.M. designed he s udy. R.F.K., G.I.R. and M.M. collec ed he da a. K.S.
conduc ed he analyses and w o e he fi s d a . R.S. helped in s a is ical analyses.
K.S., R.F.K., A.J., R.S., G.I.R., J.K. and M.M. pa icipa ed in he in e p e a ion o da a.
R.F.K., A.J., R.S., G.I.R., J.K. and M.M. e ised he manusc ip o impo an in ellec ual
con en . All au ho s app o ed he final e sion o he manusc ip .
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