HMG Advance Access published February 3, 2015

Human Molecular Genetics, 2015, 18

doi: 10.1093/hmg/ddv014
Original Article

ORIGINAL ARTICLE

Common polymorphisms in WNT10A affect tooth

morphology as well as hair shape
Ryosuke Kimura1, *, Chiaki Watanabe1, Akira Kawaguchi1, Yong-Il Kim2,
Soo-Byung Park2, Koutaro Maki3, Hajime Ishida1 and Tetsutaro Yamaguchi3, *

Downloaded from http://hmg.oxfordjournals.org/ by guest on December 28, 2016

1
Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Uehara
207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan, 2Department of Orthodontics, Pusan National
University Dental Hospital, Beomeori, Mulgeumeup, Yangsan, Kyeongsangnamdo 626-787, Korea and
3
Department of Orthodontics, School of Dentistry, Showa University, Kitasenzoku 2-1-1, Ota-ku,
Tokyo 145-8515, Japan
*To whom correspondence should be addressed. Tel: +81 988951211; Fax: +81 988951400; Email: rkimura@med.u-ryukyu.ac.jp (R.K.); Tel: +81 337871151;
Fax: +81 337846641; Email: tyamaguchi@dent.showa-u.ac.jp (T.Y.)

Abstract
Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation.
To date, it has been revealed that a non-synonymous polymorphism in EDAR has effects on the morphological variation in both
hair and teeth. Previous association studies have conrmed that single-nucleotide polymorphisms (SNPs) in/near THADA,
FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology. In this study, we thus examined whether these SNPs are
also associated with dental characteristics. We measured metric dental traits including crown size and also evaluated non-
metric dental traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans). DNA samples were prepared
from the subjects and genotyped for the hair morphology-associated SNPs. We observed a signicant association of crown size
with an SNP in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further examined four SNPs within and
around WNT10A, among which rs10177996 had the strongest association with dental traits. World distribution of the derived
allele in rs10177996, which is associated with larger teeth, showed that Eurasians have a higher allele frequency than Africans.
Together with previous studies on hair morphology, this study demonstrated that common variations in WNT10A have
pleiotropic effects on the morphology of ectodermal appendages.

Introduction have been used for comparisons of human populations in

Teeth are vertebrate-specic organs that are used for catching
and masticating food, for defense and for other purposes. In hu-
mans, teeth also play an important role in speech and in making
tools. Depending on dietary specialization and other factors, den-
tition patterns vary between species. Therefore, dental charac-
teristics have been the object of study in a wide range of elds,
including ecology, comparative morphology and paleontology.
In particular, dental characteristics have greatly contributed to
the phylogenetic reconstructions in studies of primates including
ancient hominids. Moreover, variations in detailed dental traits
anthropology.
Technological advances in the past two decades have rapidly
elucidated the mechanisms of tooth morphogenesis. Skin ap-
pendages including teeth, hair and exocrine glands such as
sweat, mammary and salivary glands are of ectodermal origin.
Although these ectodermal organs diverge greatly in shape and
form, the early stages in their development are highly similar de-
pending on inductive epithelialmesenchymal interactions (13).
Our knowledge on the molecular basis of the development of
ectodermal derivatives is based on studies of gene expression

Received: September 2, 2014. Revised: January 4, 2015. Accepted: January 16, 2015
The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

1
 2 | Human Molecular Genetics

proling, animal mutants, transgenic animal experiments and

9.3E04
7.0E01

5.5E02
9.1E01
9.1E01
human genetic disorders (47). Several genes are known to be
commonly involved in their development, and dysfunctional

P
Combined
mutations in one related gene can result in anomalies in several

0.149
skin appendages.

0.018

0.087
0.005
0.005
Owing to recent genotypephenotype association studies,

there has been increasing knowledge on genetic factors that ex-
plain phenotypic variations in human morphological traits. Pre-

2.9E03
3.3E01

9.3E01
8.7E01
3.2E01
vious studies have identied that a non-synonymous variant of
EDAR, which encodes a key molecule in the appendage develop-

P
ment, is associated with tooth morphology, such as tooth size,
shovel-shaped incisors and the number of molar cusps, as well

0.199
0.066

0.006
0.011
0.067
as hair thickness in Asian populations (811). Genome-wide as-
sociation studies (GWASs) for hair morphology have conrmed

that single-nucleotide polymorphisms (SNPs) in or near TCHH,

Korean
Freq. D
THADA, FRAS1, WNT10A and NAF1 are associated with curly

0.946
0.304
0.266
0.072
0.899
hair in people of European ancestry (12,13). An SNP in FGFR2
has also been shown to be associated with hair thickness in
Asian populations (14). Like the EDAR polymorphism, hair

1.6E02
6.7E01
8.1E02

9.8E01
3.0E01

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morphology-related SNPs may be associated with the morph-
ology of teeth or other organs of ectodermal origin. In this

P
study, we aimed to clarify whether SNPs previously reported to
be associated with hair shape are also involved in crown size

0.146
0.026
0.107

0.001
0.063
and other dental traits.

Japanese
Results

Freq. D

0.959
0.208
0.287
0.048
0.892
Of the ve examined SNPs that are reportedly associated with
hair morphology, two SNPs, rs6732426 and rs6840361, had a rela-
tively low minor allele frequency (<10%) in Korean and Japanese

Derived allele (D)

subjects (Table 1 and Supplementary Material, Table S1). Allele
frequencies did not differ markedly between the two sets of sub-
jects. Observed genotype frequencies did not show signicant
deviation from HardyWeinberg equilibrium after Bonferroni cor-
rection (Supplementary Material, Table S2). Based on regression Ta
G
G
C

T
analysis (Table 1), we found that crown size (Z[GMall ], see Materials
and Methods) was associated at P < 0.05 with rs1268789 located in
Ancestral allele (A)

FRAS1 among the Japanese subjects and with rs7349332 located in

WNT10A among the Korean subjects. In the combined set, only
Table 1. Association between hair-associated SNPs and crown size (Z[GMall ])

rs7349332 in WNT10A had a signicant association with Z[GMall ]

(P = 9.3 104), even after Bonferroni correction (P < 0.01) (Table 1).
The negative value indicated that the increased number of the
Aa

Ga
Ca
Ta
C

derived allele is associated with the decreased size of teeth.

As these examined SNPs were simply genetic markers in pre-
Allele reportedly associated with thin (rs4752566) or curly (others) hair.
Intergenic

vious GWASs, it is unclear whether these are causative SNPs

Location

themselves or are only in linkage disequilibrium (LD) with the

Intron
Intron
Intron

Intron

true causative SNPs elsewhere. To capture candidates of the

causative polymorphism, we further examined four additional
SNPs within and around WNT10A (Table 2). The ve WNT10A
WNT10A
THADA

SNPs were in strong LD with one another (Fig. 1), and four of
(NAF1)
FRAS1

FGFR2
Gene

these SNPs were associated with crown size at P < 0.05. Of these
SNPs, an intronic SNP, rs10177996, had the strongest association
(P = 2.6 104 in the combined set); the number of derived alleles
15159491921

(T) in rs10177996 was associated at P < 0.05 with increased crown

211610963

116898581
43322995

75027015
Position

size in both the Japanese and Korean subjects (Table 2). This SNP
had similar effects between mesiodistal (MD) and buccolingual
(BL) diameters, between upper and lower teeth, and between an-
terior and posterior teeth (Table 3). The effects of rs10177996 on
Chr

non-metric and orthodontic traits are also summarized in Ta-

10
2
2
4
4

bles 3 and 4; this SNP was found to be associated (at P < 0.05)
Bold, P < 0.05.

with multiple traits, such as maxillary length, shoveling in

rs6732426
rs7349332
rs1268789
rs6840361
rs4752566

upper 1st incisors (UI1), distolingual cusp in lower 2nd premolars

(LP2), 5th cusp in upper 1st molars (UM1) and hypoconulid in
rs

lower 2nd molars (LM2).

a
 Human Molecular Genetics | 3

Previous studies have been reported that rs3827760 in EDAR is

3.4E02

2.6E04
9.3E04
1.4E02
1.1E01
associated with crown size and several non-metric traits. There-
fore, we examined the joint effect of EDAR and WNT10A SNPs on

P
Combined
dental traits (Table 5). When the effect of the EDAR SNP was con-

0.096

0.165
0.149
0.112
trolled in the multiple regression, the standardized regression co-

0.072
efcient () for the WNT10A SNP (0.177, P = 8.2 105) increased in

comparison with that in the simple regression (0.165, P = 2.6
104) (Tables 2 and 5). The coefcient of determination was

1.7E03
2.9E03
3.1E02
2.5E01
4.6E01
0.064, which indicates that these two SNPs explain 6.4% of the
overall variance in crown size.
P

Figure 2 shows the world distribution of the alleles of WNT10A

0.213 SNPs. We found that the allele frequencies of rs10177996 were
0.199
0.147
0.080
0.051

highly differentiated between Africa and Eurasia, whereas

those of rs7349332, which has previously been reported to have

one of the strongest associations with the hair morphology,

Korean
Freq. D

were not markedly differentiated. However, in the comparison

0.547
0.479
0.662
0.304
0.593

with the distribution of max FST, the interpopulation differenti-

ation at rs10177996 was not extremely high (Fig. 3).
4.0E02
8.0E02
1.5E01

8.1E02
1.7E01

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Discussion
P

Only a few genetic factors have been identied as being asso-

ciated with common variations in tooth morphology to date
0.126
0.107
0.088

0.107
0.083

(10,11,15). In the present study, we demonstrated that WNT10A

polymorphisms are signicantly associated with tooth morph-

ology, including crown size and other metric and non-metric

Japanese

traits. The WNT10A gene is a member of the WNT gene family

Freq. D

0.653
0.323
0.778
0.208
0.670

(1618). WNT paracrine signaling molecules form a family of evo-

lutionarily conserved glycoproteins with at least 19 members in
humans and mice. These molecules regulate cell patterning
Derived allele (D)

during embryogenesis through a cell-surface receptor (Frizzled

low-density lipoprotein receptor-related protein complex) and a
Table 2. Association between SNPs in the WNT6 and WNT10A gene region and crown size (Z[GMall ])

transcriptional regulator (-catenin) (19,20). From experiments

in mice, Wnt10a is thought to play a role in the differentiation
of odontoblasts, the production of the dentin matrix and the
A

A
C

T
T

morphogenesis of cusps (2123). In humans, dysfunctional

WNT10A genes caused by non-sense, missense and translation
Ancestral allele (A)

termination mutations result in several forms of ectodermal dys-

plasia, including odont-onycho-dermal dysplasia (OODD), which
is a rare autosomal-recessive syndrome exhibiting severe hypo-
dontia, sparse hair, smooth tongue with reduction of fungiform
and liform papillae, dystrophic nails, keratoderma and hyperhi-
drosis of palms and soles, and hyperkeratosis of the skin (2429).
G
G

G
C
C

Moreover, many studies have shown that WNT10A mutations are

5 anking

associated with non-syndromic tooth agenesis including hypo-

Location

dontia [missing up to ve permanent teeth, excluding 3rd molars

3 near
Intron

Intron
Intron

(M3)] and oligodontia (missing six or more and missing six or

more permanent teeth, excluding M3) (3035). WNT10A muta-
tions causing severe phenotypes like ectodermal dysplasia and
WNT10A
WNT10A
WNT10A
WNT10A

non-syndromic tooth agenesis are rare in the general population.

WNT6

denotes the standardized regression coefcient.

Gene

We found that common variants in WNT10A have modest effects

on dental traits, as well as hair morphology.
Dysfunctional mutations in EDA, EDAR and EDARDD result in
211586671
211598381
211601068
211610963
211617230

hypohidrotic ectodermal dysplasia (36). It has been reported that

Position

a non-synonymous variant of EDAR (rs3827760) is associated

with common variation in the hair and tooth morphology and
in the density of sweat glands (811,37). Regarding tooth morph-
ology, individuals with the EDAR variant have an increased grade
Chr

of shoveling in UI1 and an increased number of cusps in LM2

2
2
2
2
2

( presence of hypoconulid). In addition, the EDAR variant is asso-

Bold, P < 0.05.
rs10177996

ciated with crown size, particularly MD diameter in anterior teeth

rs6754599
rs3806557

rs7349332
rs4574113

(10,11). In the present study, WNT10A polymorphisms were also

associated with crown size, and EDAR and WNT10A SNPs ex-
rs

plained 6% of the variance of crown size. However, in contrast

 4 | Human Molecular Genetics

Table 3. Association of WNT10A rs10177996 with dental traits based on linear regression

Trait b P Covariates included

Z[MDall ] 0.168 0.147 1.2E03

Z[BLall ] 0.179 0.154 7.1E04
Z[GMupper] 0.197 0.157 5.5E04
Z[GMlower] 0.215 0.167 2.4E04
Z[GManterior] 0.211 0.159 4.5E04
Z[GMposterior] 0.197 0.150 9.8E04
Maxillary length 0.429 0.096 3.9E02 Sexa, populationa, age
Maxillary breadth 0.235 0.043 3.4E01 Sexa, population, age
Mandiblar length 0.123 0.029 5.3E01 Sexa, populationa, agea
Mandiblar breadth 0.004 0.001 9.9E01 Sexa, populationa, age
Shovel UI1 0.163 0.139 3.1E03 Sex, population
Double shovel UI1 0.023 0.020 6.7E01 Sex, population
Carabellis cusp UM1 0.132 0.088 7.1E02 Sex, population
Carabellis cusp UM2 0.039 0.049 3.1E01 Sex, population
Malocclusion 0.010 0.008 8.5E01 Sexa, populationa

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b and denote the regression coefcient and the standardized regression coefcient, respectively.
a
Signicantly associated covariates.
Bold, P < 0.05.

Table 4. Association of WNT10A rs10177996 with dental traits based on logistic regression

Traits b OR P Covariates included

Tuberculum dentale UI2 0.245 0.153 1.28 3.4E01 Sex, population

Tuberculum dentale C 0.310 0.194 1.36 2.0E01 Sexa, population
Distolingual cusp LP2 0.560 0.353 1.75 1.4E03 Sex, population
5th cusp UM1b 1.173 0.773 3.23 2.4E03 Sex
Hypocone UM2 0.005 0.003 1.00 9.7E01 Sex, population
Hypoconulid LM2 0.460 0.300 1.58 8.2E03 Sex, population
Groove pattern LM2 0.286 0.182 0.75 3.1E01 Sex, population

b and denote the regression coefcient and the standardized regression coefcient, respectively.
OR, odds ratio.
a
Signicantly associated covariates.
b
Only Korean samples were available.
Bold, P < 0.05.

Table 5. Joint association of WNT10A rs10177996 and EDAR rs3827760 with dental traits

Traits Model WNT10A rs10177996 EDAR rs3827760 R2

b P b P

Z[GMall ] Linear 0.217 0.177 8.2E05 0.271 0.191 2.1E05 0.064

Shovel UI1 Linear 0.166 0.143 1.3E03 0.428 0.319 1.9E12 0.118
Hypoconulid LM2 Logistic 0.511 0.333 3.3E03 0.529 0.290 9.2E03 0.032

b and denote the regression coefcient and the standardized regression coefcient, respectively.
R 2, coefcient of determination.

to the EDAR variant, the WNT10A variant acted equally on all
teeth. Such differences in the effects of EDAR and WNT10A poly-
morphisms may be dependent on where and when these genes
act during tooth development. Our ndings provide a hint to elu-
cidate detailed molecular mechanisms for the development of
human dentition.
In the present study, rs10177996 showed the strongest signal
of the association with dental traits. However, GWAS has a limi-
tation in determining the causative polymorphism. Since
rs10177996 is in complete LD with several SNPs (rs2385199,
rs10932786 and rs4674347) in Asian populations, there remains
a possibility that another polymorphism is the real causative
polymorphism. Therefore, further studies are necessary to verify
the functional effects of WNT10A polymorphisms.
The examined SNPs in or near THADA, FRAS1, NAF1 and FGFR2,
which are reportedly associated with hair morphology (12,13), did
not show any signicant associations with dental traits in our
study. This suggests that these hair-related genes do not function
in tooth development and/or that the causative polymorphisms
do not affect gene regulation in teeth. Although we examined
hair-morphology-related SNPs as strong candidates in this
study, further association studies using genome-wide SNPs will

Figure 1. LD coefcients between pairs of WNT10A SNPs.
Figure 2. World distribution of alleles in WNT10A SNPs. (A) rs7349332 and (B)
rs10177996. Allele frequencies are based on the Human Genome Diversity
Project (http://hgdp.uchicago.edu/).
Human Molecular Genetics | 5
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be indispensable for complete understanding of the genetic basis
of variations in human dental traits. For future GWASs on dental
traits, we need to increase sample size to facilitate multiple com-
parisons in statistical tests.
Variations in tooth morphology have been emphasized in
classical anthropological studies; each individual has teeth of dif-
ferent size and shape, and each population has typical character-
istics (3841). For example, East Asians and Native Americans,
compared with Southeast Asians, are characterized as having
larger teeth, shovel-shaped UI1 and LM2 with ve or more
cusps. These East Asian- and Native American-specic dental
characteristics are often referred as sinodont, in contrast to
the opposite characteristics, sundadont (42,43). Such interpopu-
lation differences in dental characteristics can be partly ex-
plained by EDAR variants (10,11). Turning our attention to the
distribution of WNT10A SNPs, we found that rs10177996 is differ-
entiated between African and Eurasian populations; the derived
allele (T), which has an association with increased crown size, is
minor in African populations but major in Eurasian populations
(Fig. 2). Therefore, it is possible that rs10177996 contributes to in-
terpopulation differences in the tooth morphology. However, it
has been reported that African populations have larger crown
size than European and Asian populations (40), which is incon-
sistent with the distribution of rs10177996 alleles. This implies
that other genetic factors are involved in the differences in dental
traits between African and Eurasian populations. The allele fre-
quency distribution of rs10177996 seems to be consistent with
global patterns of hair phenotype distribution in which Africans
tend to have curlier hair than Eurasians. Previous reports have
shown that rs10177996 is also signicantly associated with hair
phenotype, although rs7349332 has the strongest association in
the WNT10A region (12,13). To understand pleiotropic effects
and evolutionary processes of WNT10A polymorphisms, it is
essential to study their detailed functions including effects on
tissue-specic expression as well as functional interaction and
independency of the polymorphisms.
 6 | Human Molecular Genetics
Figure 3. The level of genetic differentiation. (A) CHB + JPT versus YRI. (B) CEU
versus YRI. FST at rs10177996 (circle) and the cumulative distribution of max FST
(dots) are shown. The dashed line indicates the top 5%.
Since the EDAR variant shows one of the strongest signals of
selective sweep in Asian populations (44,45), it is plausible that
the WNT10A variant is also under positive selection. However,
our whole-genome FST analysis demonstrated that the allele fre-
quency of rs10177996 is not extremely differentiated between po-
pulations. In addition, previous genome scans for selective
sweep based on the haplotype diversity did not observe any sig-
nicant signature of recent positive selection in the WNT10A
gene region (4447). Nonetheless, a conclusion should be drawn
carefully since it is difcult to detect positive selection on a
standing variation, which is called as soft sweep (48).
The genetic basis of human phenotypic variations has just
started to be elucidated. As with the WNT10A and EDAR SNPs,
there may be numerous genetic polymorphisms with pleiotropic
effects on multiple traits. As a large-scale genetic analysis is now
feasible, exhaustive phenotypic examinations of a large number
of individuals will be necessary for better understanding the
functional and evolutional aspects of human variation.
Materials and Methods
Study subjects and dental characteristics
As described in previous reports (11,15), plaster casts of perman-
ent dentition and blood, buccal mucosa or saliva specimens for
DNA preparation were obtained from 272 Japanese individuals
at Showa University Dental Hospital, Tokyo, and from 226 Korean
individuals at Pusan National University, Pusan. The Japanese
subjects were patients undergoing orthodontic treatments, and
these individuals might not be considered as representatives of
the general population with regard to dentition. All subjects
gave written informed consent for participation in this study.
This study was conducted under the approval of ethical commit-
tees of Showa University, Pusan National University and Univer-
sity of the Ryukyus.
The MD and BL crown diameters of upper (U) and lower (L)
teeth including 1st and 2nd incisors (I1 and I2), canines (C), 1st
and 2nd premolars (P1 and P2), and 1st and 2nd molars (M1 and
M2), except for 3rd molars (M3), were measured with a sliding
caliper. The geometric mean of MD and BL diameters was calcu-
lated for each tooth and was used as an index of crown size.
Values of left and right homologous teeth were averaged unless
a tooth on only one side was available for measurement. If
teeth on both sides were absent, the value was considered miss-
ing. The length and breadth of maxillary and mandibular dental
arches were also measured. The results of the metric measure-
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ments are summarized in Supplementary Material, Tables S2
and S3.
To correct for sexual differences in crown size, we standar-
dized the values into z scores for each sex in each population
and then merged the scores. The z scores of different teeth
were averaged for each individual to evaluate the MD and BL dia-
meters and the geometric mean for all teeth (Z[MDall ], Z[BLall ] and
Z[GMall ], respectively). We also calculated the geometric mean for
subsets of teeth, that is, upper (Z[GMupper]), lower (Z[GMlower]),
anterior (I1, I2 and C; Z[GManterior]) and posterior (P1, P2, M1 and
M2; Z[GMposterior]).
We evaluated non-metric traits such as shoveling and double
shoveling in UI1, tuberculum in UI2 and UC, distolingual cusp in
LP2, 5th cusp in UM1, hypocone in UM2, Carabellis cusp in UM1
and UM2, and hypoconulid and groove pattern in LM2, based on
the Arizona State University Dental Anthropology System
(ASUDAS) and other methods with modications (Supplementary
Material, Table S4) (11,15,49). In addition, we observed malocclusion
based on Aesthetic Component in the Index of Orthodontic Treat-
ment Need (50). The results of non-metric grading are summarized
in Supplementary Material, Table S5. The Japanese orthodontic pa-
tients included a larger proportion of individuals with malocclusion
than the Korean volunteers in the present study and the East Asian
population in previous studies (51,52).
SNP genotyping
Using TaqMan genotyping assays (Life Technologies Japan, Tokyo),
we genotyped ve SNPs that were shown to be associated with hair
straightness/curliness in European populations (rs6732426 in
THADA, rs1268789 in FRAS1, rs7349332 in WNT10A and rs6840361
near NAF1) (12,13), and with hair thickness in Asian populations
(rs4752566 in FGFR2) (14). We did not genotype for rs11803731
in TCHH, which is a non-synonymous SNP that showed the stron-
gest association with hair morphology in European populations
(13), as this SNP is reported to be monomorphic in Asian popula-
tions of the Human Genome Diversity Project (HGDP) panel
(46,53). After the rst analysis, we additionally selected four SNPs
within/around WNT10A (rs6754599, rs3806557, rs10177996 and
rs4574113) based on LD estimated from the data of the Internation-
al HapMap Project (http://hapmap.ncbi.nlm.nih.gov/) (Supplemen-
tary Material, Fig. S1). LD coefcients, D and r 2, were calculated and
visualized using Haploview (54). Chi-square test was used to iden-
tify any deviation from HardyWeinberg equilibrium in genotype
distributions.

Association analysis
Association between genotypes and phenotypes was evaluated
using regression analysis. Genotypes were denoted by the number
of the derived allele, i.e. 0: homozygotes for the ancestral allele
(AA); 1: heterozygotes (AD) and 2: homozygotes for the derived
allele (DD). Linear regression analysis was performed for examin-
ing metric traits and non-metric traits that were shown by
continuous and ordered variables. Dichotomized non-metric
traits were tested by logistic regression analysis. The Japanese
and Korean sets were separately or combinedly examined.
Depending on the tested trait, covariates such as sex, population
and age were included in the model. We also evaluated the joint
effect of multiple SNPs with dental traits, where previously re-
ported data for the EDAR genotype were included (11).
Analysis of genetic differentiation among populations
World distribution of the allele frequencies for rs7349332 and
rs10177996 in WNT10A were downloaded from the HGDP Selection
Browser (http://hgdp.uchicago.edu/) (46,53). The level of interpo-
pulation differentiation at rs10177996 was evaluated in the com-
parison with the whole-genome SNPs using the Phase II data of
the International HapMap Project (55). We used data of unrelated
individuals from Yorba in Ibadan, Nigeria (YRI), people of northern
and western European ancestry in Utah (CEU), Han Chinese in Bei-
jing and Japanese in Tokyo (CHB + JPT). FST values (CHB + JPT ver-
sus YRI and CEU versus YRI) were calculated for all the SNPs.
Then, we divided the whole genome (excluding sex chromosomes)
into 50 kb windows and obtained the maximum value of FST (max
FST) in each window. FST values at rs10177996 were compared with
the distribution of max FST, excluding windows with less than ve
SNPs.
Supplementary Material
Supplementary Material is available at HMG online.
Acknowledgements
We are deeply grateful to all those who participated in this study.
We thank M. Takeda for assistance in taking measurements and
Y. Tomoyasu and M. Watanabe for assistance in sample
collection.
Conict of Interest statement. None declared.
Funding
This work was supported by KAKENHI Grant-in-Aid for Young
Scientists (A) (22687023 to R.K.) and Grant-in-Aid for Scientic
Research (B) (22390393 to T.Y.) from the Japan Society for the
Promotion of Science.
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