70, 15611568

International Journal of P ediatric Otorhinolaryngology (2006)

www.elsevier.com/locat e/ijporl

Recurren t otitis media and tonsilli tis: common

disease predis position
b
d,c
Ellen Kvestada *, , Kari Jorunn Kv r ner
, Espen Ry s amb
,
d
a
a
Kristian Tambs , Jennifer Ruth Harris , P er Magnus
a

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

Department of Otorhinolaryngology, Akershus University Hospital, University of Oslo, Norway
c
Department of Psychology, University of Oslo, Norway
d
Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway
b

R eceived 24 January 2006; received in revised form 8 April 2006; accepted 10 April 2006

KEYW ORDS
Otitis media;
Tonsillitis;
Comorbidity;
Upper respiratory
infection;
Genetics;
Twin study

Summary
Objective:To estimatethe relative contributionof genetic and environmental
effects to the association between recurrent otitis media and recurrent tonsillitis.
Methods:Self-reportquestionnairedata from a population-based
cohort of 9479
Norwegiantwins born from 1967to 1979.R ecurrentotitis media and recurrent
tonsillitiswere main outcomemeasures.Structuralequationmodellingwas used
to t alternativebiometric models to the twin data and to estimate
the relative
contribution of genetic and environmental effects to the association between otitis
media and tonsillitis.
Results:The lifetime prevalence was 11.7% (95% CI: 11.012.3) for recurrent tonsillitis and 11.2% (95% CI 10.511.9) for recurrent otitis media. Tetrachoric correlations were greater in monozygotic than in dizygotic twins in both males and females. A
model specifying additive genetic effects and individual environmental effects for
otitis media and tonsillitis and non-additive genetic effects for tonsillitis yielded the
best t. There was no evidence for sex differences in the genetic source or magnitude
of the genetic effects. There was a substantial overlap in genetic factors inuencing
variation in liability to otitis media and tonsillitis.
Conclusion:Common genetic factors contribute substantiallyto comorbidity
between recurrent otitis media and recurrent tonsillitis.
# 2006Elsevier Ireland Ltd. All rights reserved.

* Corresponding author at: Division of Epidemiolo gy, Norwegi an Institute of Public Health, Pb 4404 Nydalen, N - 0403 Oslo, Norway.
Tel.: +47 23408209; fax: +47 23408252.
E-mailaddresses:
ellen.kvest ad@fhi.no (E. Kvestad), k.j.kvarner@medisin.uio.no (K.J. Kvrner), espen.roysam b@psykologi.uio.no
(E. Rysam b), kristian.tambs@fhi.no (K. Tambs), jennifer.harris@fhi.no (J.R. Harris), per.magnus@ fhi.no (P. Magnus).
0165-5876
/$ see front matter
# 2006Elsevier Ireland Ltd. All rights reserved.
doi: 10.1016/j.ij porl.2006.0 4.004

1562

E. Kve stad et al.

estima te the proport ion of genet ic and environm ental effects that are commo n and spe cic to the two
Otitis me dia is an infec tious disea se, resul ting pheno
from types.
the interpla y betw een micr obial load and imm une
respo nse. The high inciden ce and the high rate of
spont aneous
re coverysuggestthat otitis media 2. M aterials and methods
could be conside red part of the natura l mat uration
of the imm unologic al syste m in childre n [1] . 2.1. Sample
As earl yas 1957upperrespirat orydisea sewas
consid ered to play an impo rtant role in the aetiology
The Nor wegia n Institute of Publi c Health Twin Study
of middle ear disea se [2] sugge sting that the whole
is a dyna miccoho rtstudy. The cur rentdata base
respi ratory tract, includin g the middle ear, should
includesinfor mationon twins born in 1967197 9
be seen as a unit liable to the same phys iologic al
identi ed thro ugh the Medical Birth R egist ry of Norchan ges.The close relations hipbetw eenotitis
way. The R egio nal Ethics Comm ittee re viewed the
media an d tonsillitis has been demons trated in study.
more Two ques tionnaire
studieshave been conrecent epidemi ologica l studie s [35] . I n addi ducte
tion, ad,in 1992(q1) and 1998(q 2)
wit hindividu al
prosp ectivestudy of pre schoolchild ren[5] sug- respo nse rat es of 73% and 63% and pair w ise re sponse
gested that tonsillar infecti ons acco mpany comm
on of 64% and 52%, re spectiv ely. The q1 was se nt
rates
colds in somechildren, w hileothersseemto be
to all twins born during19671 974,
w ho w ere
at
pred isposedto subseq uentmiddl eear disease. least 18 yea rs old and for w hom a cur rent add ress in
Kvaerne r et al. re ported a mo derate but signica
nt
Norway
was obt ained. The q2 was sent to all twi ns
associa tion betw een recurren t ot itis med ia and
tonreceiving
q1, plus to ve new birth cohorts includin g
silliti s bot h in a cross-s ectional study of preschool
twins born during 19751 979. Th e combin ed q1 and
child ren [4] and a in a retrospect ive ques tionnaireq2 sample includes 9 479 twins who responded to at
based study of Nor wegian twins [3] . These analleast
yses,one of the ques tionnaires. 4 430 twins part iusing twin data from a sub sample of the pre sentcipate d in both studie s. Table 1 shows the num ber of
study populat ion,did not explo rethe exte ntto
pairs part icipat ing in the q1, q2 and the combi ned
which the ass ociationbet weenotitis media and
sampl e by sex and zygo sity. In q1 and q2 the re were
tonsill itiswas attrib utableto commo ngeneticor
724 and 1377 pairs from whom onl yone twin
enviro nment al facto rs. A substanti al genet ic predisrespo nded,re spectiv ely.P airswhere one twin
posit ion for otit is med ia [68] and tonsille ctomy
[9] nded to q1 and the co-tw in responded to q2
respo
has previou sly been reporte d. Herita bility estima
or tes
vice -versa are treate d a s pai r respo nders in the
of otitis me dia [10] and to nsillitis [11] based on combin
the
edsample. Th e twi n r e searchprog ram,
prese nt study popu lation has also pre viously been
includin gprocedu res
and zygositydete rminatio n,
report ed. Genetic effects , compr ising bot h addiistive
descri bed in det ail elsewhe re [12,1 3] .
and non- additive effects, expla ined 62% of the liability to recur rent tonsill itis and there were no sex
2.2. Measures
differe nces in the genet ic source or in the size of the
genet ic effects. R egardi ng ot itis med ia, the heritBoth ques tionn aires
includedthe foll owingitem s
ability compr isedonly addi tivegene ticeffects.
aboutear infec tionsand tonsill itis:Do you have
There w ere no sex differen ces in the genetic source
but a slightly g reater genet ic effect in males (0.72)
Table 1 Number of pair responders by sex and zygosity
compa red to fem ales (0.61) w as suggest ed. A mo
del
withou t these sex differen ces,w here genet ic
Group
Q1
Q2
Combined
a
effects explaine d 66% of the disea se variabi lity in
pairs(N)
P airs(N)
sample
pairs(N)
both males and femal es, gave almo st equiv alentMZM
t
416
526
677
to the data. The utilisa tion of twin studi es to esti-MZF
528
777
904
mate the genet ic and enviro nmental causes of covDZM
387
397
592
ariatio ncontribu testo bette runde rstanding
of
DZF
443
655
789
upper respirator y comorbid ity.
DZU
796
979
1285
total
2570
3334
4247
The pre sentstudy address esthe ques tionof
shared aetiolo gy in otitis media and tonsillitis , using
Q1, 1992 questionnaire; Q2, 1998 questionnaire; MZM, monozygotic
a bivar iate twin des ign. Th e aim of our study was
to males; MZF,monozygoticfemales;DZM, dizygoti c
DZF, dizygoti c females; DZU, dizygotic unlike sex.
invest igate w hether shared genet ic or environmmales;
ena
The combined sample includes twins who have responded
tal factorscontr ibuteto the associa tion
betw een
to either questionnaire 1, questionnaire 2 o r both.
otitis me diaand tonsillitis. Furthe rmore,we will

1. Introduction

R ecurr ent otitis me dia and to nsillitis: comm on disea se pre dispos ition

1563

or have you had re current tonsillit is? Do youindividualdifferencesin

have
phenotypesb yutil izin g
or have you had recur rent infections in the ear?obs
If
erved sta t is tics on a nalys is o f va ri at ion wit hin
yes, what w a s the age of onset of the rs t infecan d b et ween t win pairs [14] . Twin r esemblan ce f o r
tion? Th erespo nders
were askedto provid ethe
ot iti s media a nd t ons illi tis , re specti vely, can a rise
speci c age of onset of th e rst ear infe ction and
from
theshared genes, s hare d e nvironments, or both.
rst tonsillit is. For this study, we ass ume that those
Iden tical t wins sh are a ll their genes, w hile fraterwho report recurre nt ear infecti ons and/or recur-nal twins, on average,s harehalf of their segrerent tons illitis at lea st once have had th e disease.
gating genes. C onsequently,gene tic effects
Acco rdingly, all individ uals reporting recurren t ear
cont ri bute
to sim i la rity
am ongm ono zygoti(MZ)
c
infec tions and /or recurre nt tonsillitis in at least pai
oners, but c ontribut e t o s im ilarit y an d differences
ques tionnaire
were incl udedas cases .Usingthe
am ongdizygot ic(DZ)pa irs.Th ep o ssi ble
gen etic
clinica l criterion of sev en years or youn ger for age
an d environmental effects t h a t c ontribute to t he
at onset of re currentear infec tions,onl ythose phenotypic v arianceb etween in d i viduals
a re
individ uals reporting the disea se before age seven
s h o w ninth epa t hdi a g r a min Fi g. 1 .
were included as cases , since rec urrent otit is media
Geneti cfactorscompris e
addi tive(a) and nonis most comm on in presch ool childre n. R espond
addi
ents
tived)
( effects , where
a re fers to the addi tive
with re currentear infe ctions and missing data
on
effect of alleles at several loci, d
and
refers to geneage at onset were included in the an alyses as cases.
interac tions
th atcan be either dom inance
(intr alocus intera ction)effects or epistas is(inter-l ocus
interac tion).In dominanteffec ts,one allele has
2.3. Analysis
more in uence on pheno typic expr ession at a part i2.3.1. Analyt ical issu es usi ng categori cal twin cular loc us, and epist asis is the sum of interacti on
effects between diffe rent loci. Data on twins alone
data
Every individual s phenotype is made u p of gencann
etic ot resolve the contr ibutio n of dom inance and
epistas is to non -additive genet ic effects, but must
an denvi r o nmen con
t al tributi onsTw
. indat acan
be supplem ented
by extendedfami liydata [15] .
be used to determine the exte nt to which g en etic
an denvironme ntal
diff e r enceare
s i mportantf o r Environm ent al factors are part itioned into comm on

Fig. 1 P ath model depicting the contribution of genetic and environmental factors to twin resemblance. P denotes the
phenotype. A, D, C and E are latent variables for effects of genes acting additively, genetic dominance, environmental
factors shared by cotwins and individually acting environmental factors, respectively. Lowercase letters denotes the
corresponding path coefcients for the contribution of the latent variables on the phenotype. The genetic additive
cotwin correlation is unity for monozygotic (MZ) twins and 0.5 for dizygotic (DZ) twins. The cotwin correlation between
genetic dominance is unity for monozygotic twins and 0.25 for dizygotic twins.

1564

E. Kve stad et al.

(c) and spec ice)( enviro nment. Common envi roninstanc e, th ereare no effec tsof genet icdom imen t ref ers to environm ental factors shared bynanc
the e or commo n envi ronm ent )
bemay
statist itwins , thu s contributi ngto twin resemb lance cally compared with the observed data. A num ber of
regardle ss
of zygosity.Earl yinfec tiousexpos ures, mod els can be tte d t o the data, and the t of the
2
num ber of siblings, type of chi ld-care arr angeme
mod
nt el is assessed by a goodne ss-of-t
x -test. The
and breast -feeding pattern are norm ally examplgoal
es in mo del tting is to explain the observed data
of shared enviro nmental effec ts in childhoo d. The
as well as possib le.
non-sh ared enviro nmental effects
e) are( exposur es
The nal step in twi nanalysesis to esti mate,
that are not shared by the members of a pair, that
based on the best-t ting mo del, th e proport ion of
cause w ithin-pai r diff erences for a trait and includes
varianc e in liabil ity to otitis me dia and to nsillitis,
2
meas ureme nt error.
respec tively,
due to add itivegenet icactio n(a ),
2
Simple correlati oncompa risonscan indicate non-add itive g enetic effects
d ), (comm on envi ron2
whet her genet ic in uence is import ant for a trait.
men tal effectsc (), and ind ividual- specic envi ron2
Co-twi n simila rity for otitis me dia and to nsillitismen
can te( ). The propo rtion of varianc e in liabilit y due
2
be measur ed by estima ting tetrachor ic correla to
tions.
the sum of additi ve genet ic effects
a ) and
( non2
The tetrac horic co-twin correla tion rep resents the
addi tive effec ts
d )( is termed heri tability. Furthe r
correla tionbet weeneac h oft h e co-tw in
unde
s r- detail sof the applica tionof biome tricalgenet ic
lying liabilit y t o disease. This model fur ther assu
mod
mes
els are outli ned elsewhe re [16] .
that otitis mediaor tons illitis,respecti vely, has
a
Equali ty of prevale nces for ot itis me dia and tonmultifa ctorialaetiology involvin ga number of
silliti s, re spectiv ely,
w ithintwin pairs, betwe en
genet icand envi ronm ental
risk factors of low to
gender gro ups, between zygo sitygro upsand
mod erate effects. Und er these circums tances, the
betwe en compl ete and incomp lete pai rs, was tested
distrib utionof the liabi lityof the diseasein the
before we started the mod el-ttin g procedu re. Sevgenera l populat ion may be assu med to be app eral
roxi-mod els were t to es timate the si gnican ce of
mate ly normal [14] . Tetracho ric correla tions were
speci c para meters . The obs erved patte rn of mo noestima ted in ve gro ups, dened by sex and zygo
zygotic
sity and diz ygotic twin correla tions indicates the
(i.e. monoz ygoticmales, monozy goticfemale s, degre e t o which the diff erent factors (A, C, D and E)
dizygot icmale s,dizygoticfem alesand dizygot ic are present. A patt ern of diz ygotic twi n correla tions
opposi te sex pai rs) for: (1) twi n-cotwin re semblance
highe r than hal f the monozy gotic twi n correla tions
for otit is me dia and tonsillitis, (2) the pheno typic
indicate sthat commo nenvi ronm ent
play sa role,
(withi n per son) relations hip betw een tonsill itiswhile
and dizygotic twin corr elati ons less than half the
otitis media , and (3) the cross-t win-cro ss-trait simimonoz ygotic
twin correla tionssugge sts
that the
larity (otits media in twin 1 in a pair and to nsillitis
genet
in iceffe ct may be partly non-addi tive[14] .
twin 2 in the same pai r).
Becau se
c andd cann ot be esti mated si multaneo usly
in the struct ural mo dels, either AC E or AD E is chosen
2.3.2. Model tting using Mx
as the full model based on the obs erved correla tion
patte rn.In the mo deltt ingproce duresthe full
The path mo del represe nts the hypothesi zed causal
conne ctionsw ithina systemand is a series of
mod el is compare d with neste d su b-models. A mo del
regress ion equa tions that describ e the relationswith
hipsonly non- additive g enetic effects and no addibetwe enthe tetra choriccorrela tionsand the
tive genet iceffect is not realistic becau seeven
hypothe sized
latent variable s( genotype s
and
under full dom inance most of the genet ic variance
enviro nments ) [16] . Fig. 1 represen ts the genet
will usuall
ic
y be addi tive [17] . Rat her than acce pting
path mo delfor twi nstudies,where the obs erved a model w ithoutaddi tivevariance ,d w asconcorrela tions can be descri bed as the sums of paths
strain ed not to exceed
a in the models test ed.
betwe en the phen otypes of twin1 and twin2. Iden-By meansof bivariateanalysis,the cova riance
tical twins are perfect ly corr elated for effects due
betwe en the phen otypes can to be partition ed into
to additi veand non -additive
genet iceffects ,and
genet ic and envi ronm ental compo nents. Moreover,
frater naltwi nsare correla ted0.5 for addi tive sex-spe cic effects may be invest igated w hen the
genet iceffects and 0.25 for non- additive
genet ic data incl udes infor mation from same- sex and oppoeffects in our models . Th ese effects (A, C, D andsite-sex
E)
twins [14] . Models of g eneral sex-lim itation
are used when theoret ical models are built.
specify that bot h the sourc e and the magnitu de of
To estima tethe twi ncorrelati onsand perform genet ic and envi ronm ental
effe cts may vary
the mo del-ttin procedurea
g
compute r prog ram, betwe enmalesand female s.The mo rerestr icted
such as Mx [16] , is nee ded. Mo del-tti ng approach
mod es
elof commo nsex-l imitatio only
n
allows the
involve con structing
a mo delthat descri besthe
magnitu de of the se effec ts to vary bet ween males
obser veddata. The model s pre dictions(for
and female s.

R ecurr ent otitis me dia and to nsillitis: comm on disea se pre dispos ition

1565

A seri es of models wer e tested, begi nning with

(i.e. otit is media in twin1 ver sus tons illitis in twin2).
the full mo del and alterna tive mo dels wer e tested
Twinc
in otwincorrela tionswer egeneral lyhighe r
a stepwise manner by adding constra ints. Th e goodamongmonoz ygotic
th anamon gdizy gotictwins
ness-o f-t for the differe nt mo dels w ere evaluated
indicati ng genet ic variance for both recurre nt ear
acco rding to Aka ike sInf ormation Criter ion infec tions and recurren t tonsill itis. The cross-tw in
2
(AIC =x 2df) [18] , addressingboth likeliho od cross-t rait correla tions
were, as expected,gene rand simplici tyof mod elsand allowi ngnon -nested ally lower than the twinco twin correla tions for the
mod els to be compare d. This statist ic evalua tes
same
the trait. Again, there w a sgre atersi milari ty
magni tude
of discrep ancy
betweenexpectedand
among mo nozygotic than diz ygotic twins, suggest ing
obser vedval uesby compa ringhow like ly the
that genet icfacto rscontr ibuteto the associ ation
obser ved data are unde r the model unde r evaluabetwe en the two measur es. Beca use the DZ unlik etion. If the AIC is low (i.e. non-sign icant), it indi-sex corr elations (cotw in and cros s-twin cross-t rait)
cates that the observ ed values do not signica ntly
are not si gnican tly
lower than th esame -sex
DZ
deviat efrom the expec tedval uesand the mo del correla tions, the re were no evid ence that differe nt
yield ing the lowest
val ueof AIC ts the obs erved genesor comm on envi ronment s contr ibute
theto
data best.
associa tion bet ween otit is med ia and tonsillitis
in
males and fem ales.

3.2. Model tting

3. Results

The m odeltting resu ltspre sentedin Ta b l 3,e

identies a m odelcomprisingadditiv egenetic
effects a ndunique environmentfor both otitis
The prev alenceof re currenttonsillitiswas 11.7% medi a a nd tonsi lli ti s, and i n a ddi ti o n a n on-addi (95% CI 11.0 12.3) and the prev alence of recurre
tivent
gene ticeffect for tons illi tisT. herew e r no
e
otitis media was 11.2% (95% CI 10.511 .9). There
sign sof s exdifferen c es,neither in the gen etic
were no preval ence diffe rences bet ween mo nozyso urce n
, or in the siz eof t heeffect s.Ta b l 3e
gotic and dizygot ic twins or betw een single andsh
paiows
r the s p e c ic m odel t ti ng st at is tics for t he
respo nders.
common s e x-limitati on models
(mod e l13
s )a nd
The esti mated tetra choric corr elations for otitis
no s e x-limi ta ti models
on
(mod els46). The
media and tonsillitis , sugge st a genet ic predispresults
osi- i n Ta b l 3e are presentedstarting with
tion for eac h o f the diseases ot itis me dia and tonth eleast constrainedmodel, and m oreparsimosilliti s,and a sharedgenet iccompo nent
betw een nious models a re comparedwith the f ull A DE
the two diseases. Table 2 shows pheno typic correlamodel ( model1). The si gni can ce
of th e nontions (i.e . correlati onbet weenot itismedia and
additivege neticeffect for t onsillitisis r eected
tonsill itisin the samp leof twi ns),twinco twin by the large positiveAIC v a lues
in model 3 and
correla tions(i.e. correla tionsbetwe entwin1 and
model6, excludingth isparameter.Non-additive
twin2 for each measure ) and cross-t win cross-t rait
genetic effects f or otitis me dia c o uld be d r opped

3.1. Prevalence and correlations

T able 2 P henotypic correlation, twin co-twin and crosstwin crosstrait correlations in a study of 4247 twin pairs,
according to zygosity and sex
Correlations

MZM

MZF

DZM

DZF

DZU

0.71
(0.62,0.79)
0.71
(0.61,0.79)

0.64
(0.57,0.71)
0.61
(0.52,0.67)

0.35
(0.20,0.48)
0.10
( 0.07,0.27)

0.25
(0.13,0.36)
0.14
(0.03,0.25)

0.33
(0.22,0.40)
0.24
(0.14,0.32)

Crosstwin cross
trait correlations
R ecurrent tonsillitis in twin1 0.20
versus otitis media in twin 2 ( 0.04,0.34)

0.25
(0.15,0.35)

0.12
( 0.05,0.28)

0.18
(0.06,0.29)

0.14
(0.04,0.24)

P henotypic correlations
R ecurrent otitis media
versus tonsillitis

0.43
(0.34,0.52)

0.33
(0.19,0.46)

0.37
(0.27,0.46)

0.44
(0.36,0.52)

Twinco-twin correlations
R ecurrent otitis media
R ecurrent tonsillitis

0.42
(0.29,0.53)

MZM, monozygotic males; MZF, monozygoti c females; DZM, dizygoti c males; DZF, dizygotic females; DZU, dizygotic unlike sex.

1566

E. Kve stad et al.

Table 3 Bivariate model tting statistics. All models are compared to the common sex-limitation ADE-model
Sex-limitation

Model

Common

ADE
ADtons E
AE
ADE
ADtons E
AE

No

2 times log liklelihood

25404.942
25407.051
25632.950
25411.892
25413.971
25859.378

df

Dx

37903
37906
37908
37909
37911
37912

2.109
228.014
6.949
9.028
454.435

Ddf

AIC

3
5
6
8
9

.550
<.001
.326
.340
<.001

3.891
218.014
5.051
6.972
436.435

A: additive genetic effect, D: non-additive genetic effects, E: individual environmental

: non-additiv
D
e genetic effects for
tonseffects,
2
tonsillitis only, AIC: Akaike s Information Criterion
(
All models are compared to the common sex-limitaion ADE-model.
DX 2df).

from the m odelwi thou tsubst ant ialos

l sof t.
effects inuenci ngvari ationin liability to otitis
Acco rdi ng
to AIC th e no sex-lim it at ion
AD
E
media and tonsillitis, genet icfactors expla ining
tons
model y ielded the best t.
59%of the correla tionand envi ronment factors
al
The best tt ing mod el is ill ustrated in Fig. 2 .expla
Both ining the remain ing 41%.
pheno types are in uenced by a substanti al addi tive
genet ic effect. Bro ad sense heri tability is obtai ned
by summ ing
the squaredeffects from the la tent 4. D iscussion
factors A and D and yields es timated herita bilities
of 0.66 for otitis me dia an d 0.63 for tonsillitis . The
The aim of this studywas to investiga te
w hether
resul ts from the se bivar iate analy ses are ver ysharedgenet
simila r
icand enviro nmental
facto rscontr ito thoseobtai nedunderpreviou sunivariat eanabute to the associa tion
betwe enotitis med ia and
lyses of otit is me dia [10] and tonsill itis [11] based
tonsillit
on is. Findings re vealed a sub stantial pheno tythe sam e study popul ation.Th e correla tions pic corr elati on betwe en otit is me dia and to nsillitis,
betwe enthe latent factors A and E reect the
acco unted for by genetic and non- shared envi rondegre e to which the additive genet ic and envi ronmen tal effects .
men tal factors inuenci ng ot itis med ia is associ ated
with the correspo nding facto r in uencing tonsillitis.
4.1. Limitations
These corr elati ons
betwe enthe late nt facto rs,
ra = 0.52indica teoverlap in the genet iceffects
Clearly, val idity concerns arise wit h the use of retroandre = 0.48, indicate overlap in the enviro nme ntal
specti ve self-repo rts to meas ure a histor y of child-

Fig. 2 P ath model depicting the contribution of genetic and environmental factors to the association between otitis
media and tonsillitis within one twin in the best tting model. A, D and E are latent variables for effects of genetic
additivity and dominance and non-shared environmental factors, respectively. Lowercase letters denotes the corresponding path coefcients for the contribution of the latent variables on the phenotype.
ra and re are correlations
reecting the degree to which genetic dominance, additive genetic effects and unique environmental effects inuencing
otitis media correlate with the corresponding factors inuencing tonsillitis.

R ecurr ent otitis me dia and to nsillitis: comm on disea se pre dispos ition

1567

hood infe ctious disea se. Disease class ication in

tests
thisout of all availabl e tests in the screening period
study is based on a simpl e question inquir ing abo
and
utcorr elati on coefci ents were estima ted based
ever having had to nsillitis and ear inf ections. Sevon these scores. The ques tionnaire based Norw egian
eral potentia l s o urces of bia s may inuence the
study
se [4] asse ssed
presen ceof upper respi ratory
resul ts. Selection bias may arise if individu als with
morbidi
a
ty the previou s month and the pre vious yea r
histor y of infecti ous disea se were more or less in
likely
childre naged 45yea rs.P earsoncorr elati on
to answer our questi onnaire. Comp aring the precoefci
vaents were calcula ted to asse ss the associ alence rates of tonsillit is and otitis med ia for twi ns
tions bet ween ot itis media and tonsillitis. P earson
respo nding in pairs with single re sponders , w ecorrela
found tion coe fcient may underest imate the relano evidence that re fusal to particip ate in our study
tionshi p bet ween otit is me dia and tonsill itis si nce
was syste matica lly
related to the two infec tions. estima ted on dichoto mised data [20] and the tetraR eca ll bias may pos e a pr oblem if part icipantschoric
tend correla tion has been sug gested as a solution
to forget chil dhood infec tions or regard the infecto this problem as an estima torof the true
tions a non- signica nt hea lth proble m. Acc ordingly,
correla tion[20] .In our study,we havees timated
an underrepo rt of tonsillit is and otitis med ia, orthe
only
tetra choric corr elation betwe en a dichoto mised
dete ction of the most severe cases requirin g medmeas ure of otit is media and tonsillit is an d the difical or surgic al treatme nt, cann ot be ru led out ference
in out s in me thodolog ical appro ach makes it difques tionnaire . This may in turn deate the pre vacult to direct lycompare th e resul tswit h the
lence and some what bias the heritabili ty estimaprev
tes. iously reported P earson correla tions. Kvrne r
Misclas sicat ion caused by diffe rent interpr etation
et al. [4] report that of a to tal of 3737 chil dren 78
of the term r ecurrent
ear infe ction/tons illitis reporte dboth otitis mediaan dtonsillitisand 460
mayeither inate or deatethe pre valence
estireporte done of the two infe ctions.This givesa
mate s. The estimate d heritab ility will be deated
tetrach oric correlati on of 0.43 .
and th enon- shared
enviro nment
estima te,which
also includes me asureme nt er ror, will be artic4.3.
ially Genetic and env ironmental factors
inated. Ho wever, our main focus in this study was
to unde rstand
the natureof the covarian ces, and W e foun devide ncefor a sub stantialcomm on
wherea s rando m error contr ibutes to varianc e,genet
such icpredisp osition
for rec urrentotit ismedia
error does not con tributeto the covarian ce.A
and tonsill itisthat may be related to anat omy,
broad er discus sion on the validi ty of our measur
immu
es nological
defencemechan isms
or bot h.It is
is presen ted in prev ious publi catio ns [10,1 1] .well known th atW aldeyerring
s exer tsregional
The re was a sub sta nti al as soc iat ion bet wee
immu
n lifne
e-functi onswhen expo sedto airbor neand
tim e ton sil lit is and oti tis med ia. Ta k ing int o aliment
acc oun ary
t antige ns[21] . Morpholo gicalstudie s
the cro ss -se cti on al nat ure of our dat a, the ashave
soci found
at ion signica nt change s in the local innate
mi ght be du e to a dir ec t cau sa l rel at ions hipand
bet acqu
wee nired bacte rial defence system dur ing acu te
the two dis eas es or the di sea ses may be in uen
tonsillit
ce d by
is [22] such as increase d lysozyme and laca com mon dis eas e pre dis posi tio n. The pre sen
t s rin
t udcoa
y ting of the bacteria and re duced secretofer
add res ses the qu est ion of sha red ae tio log y, tory
and the
IgA . Further, increase dcarrier rat es of
ex tent to wh ich thi s can be exp lai ned by cor rel
pathog
at ed enicbacteria are found in childre nafter
ge neti c and env ir onm en tal fac tor s. Bot h in tonsille
fec tio ns
ctomy
[23] .Lower serumimmu noglobul in
ar e to a lar ge ex tent cau sed by the sam e mi cro
level
bi solo
in -o t itis-prone chil dren compa red with chilgi cal pa tho ge ns, and vir al in fec tio ns pre ce de
dren
bac
w ter
ith -fewer ot itis media episod esis also
ial inf ect ion s in a ma jor ity of the cas es [19 ] .reporte
Thi s d [24] . A single gene locat ed on chrom osome
sug ge sts tha t the dis eas es als o mi ght , a t le10
a code
s t pars tly,
for Mannose- binding lectin, a serum proinv olv e co mmo n pat ho gen ic mec hani sms . tein that is suggest ed to play an important role in
the inn ate imm une respo nse in hum ans. A pros pec4.2. Phenotypic correlation
tive cohort study of Greenl andic chil dren [25] found
an incre ased risk of acute
upper respirat ory tra ct
The phenotyp ic corr elation w a s 0.42 bet ween infec
otitistions in children aged 6 thro ugh 17 mo nths with
a re ducedfunctio nof Manno se-bind ing
lectin .A
media and to nsillitis in these data and is rather high
compa red to other studie s which reporte d 0.18molecu
[4]
largenet icstudy [26] foun devide ncefor
and 0.19 [5] .One study[5] was basedon Dut ch linkage betwe en rec urrent otitis media and mar kers
child renwho were clin icallyscreen edevery 3
on the chr omosom al region s 10q, 19q and 3p. Co rmonth s betw een the ir second an d fourt h birthrespo
day. ndingmo leculargenet icstudi esare not
The fre quencyof otit isme diaand to nsillitiswas
reporte dfor tonsillit is,but it is suggest ed
that
expre ssed
as the proport ionof pos itivescreen ing seve ral cand idate genes in these regions that may

1568

E. Kve stad et al.

[8] M. R overs, M. Haggard, M. Gannon, G. K oeppen-Schom erus,

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R. Plomin, Heritability of symptom domains in otitis media: a
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U ,. K e h r eDn.,B at t i s t utJ .t D
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