supplemental text 1 observations of unexpected majority ...10.1038... · genetic ancestry and 24.4%...
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Supplemental Text 1. Observations of unexpected majority-genetic ancestry.
The test requisition form for our ECS lists three Asian ethnicity options (East, Southeast, and South Asian) and lists example countries of origin accompanying each option. We observed that those self-reporting as Southeast Asian typically had their majority genetic ancestry coming from the East Asian (EA) rather than South Asian (SA) component (Figure 1a, "E Asian", "SE Asian" and "S Asian" rows). There were both East Asians with majority South Asian genetic ancestry (4.7% of self-reporting East Asians) as well as South Asians with majority East Asian genetic ancestry (2.8% of South Asians). The largest proportion of individuals with majority-European ancestry (EUR) among the three Asian SREs was among the Southeast Asian group (3.9% of self-reporting Southeast Asians, compared to 2.0% of East Asians and 0.6% of South Asians). The majority genetic ancestry and self-reported ethnicity matched better for South Asians (96.3% of South Asians had majority genetic ancestry component of South Asian ancestry) compared to East Asians (93.0%).
Those self-reporting as Middle Eastern had majority genetic ancestry split mostly between Middle Eastern (59.2%, ME), South Asian (28.4%), European (10.2%) and Ashkenazi Jewish (1.7%, AJ) with the remaining ancestries each <1% (Figure 1a, "Mid. East" row). The large proportion of individuals with majority-South Asian genetic ancestry may arise from a technical limitation to strongly distinguish between Middle Eastern and South Asian ancestry when admixed with European ancestry.
Patients self-reporting as Ashkenazi Jewish had majority genetic ancestry coming from the Ashkenazi Jewish ancestry component for 80.2% of patients, from the European component for 16.8%, and from the Middle Eastern component for 2.7% of patients, with <1% with other majority-GAs (Figure 1a, "AJ" row). Since the AJ genetic ancestry distribution among the AJ is wide-ranging with a mode near 3/4 AJ genetic ancestry, those with majority-European genetic ancestry may still have substantial levels of AJ ancestry (SI Figure 1).
Self-reporting Northern Europeans had largely expected genetic ancestry, with 96.9% of Northern Europeans having majority genetic ancestry coming from the European component and 2.2% having majority-AJ genetic ancestry with the other majority-GAs at <1% of Northern Europeans (Figure 1a, "N. Eur." row).
Self-reporting Southern Europeans also had less expected genetic ancestry compared to Northern Europeans, with 84.0% of Southern Europeans having majority genetic ancestry coming from the European component, 13.5% from the Middle Eastern component, and 1.5% from the AJ component with the other majority-GAs at <1% of Southern Europeans (Figure 1a, "S. Eur." row).
For patients self-reporting as African or African-American, 90.7% had majority genetic ancestry from the African ancestry component (AF) and 6.3% had majority genetic ancestry from the European component (Figure 1a, "Afr. Am." row). As the African ancestry distribution among this self-reported ethnicity has a mode at around 80% with a secondary mode at 40%, the subpopulation with majority-European ancestry is still expected to have substantial African genetic ancestry (SI Figure 1). A subpopulation with admixture between Middle Eastern and African ancestry was also observed; 2.2% of patients self-reporting as African or African-American had majority genetic ancestry from the Middle Eastern genetic ancestry component.
Three subpopulations were observed among those self-reporting as Hispanic: 1) those with European-Native American admixture, 2) those with European-African American admixture, and 3) those with admixture from European, Native American (NA), and African sources. In this analysis, only two-way admixture was considered and those with strong evidence for more admixture sources were excluded (described in Methods). The levels of European and Native American ancestry in group (1) were wide
2
ranging, reflected in the observations that 72.1% of self-reported Hispanics had majority-European genetic ancestry and 24.4% had majority-Native American genetic ancestry (Figure 1a, "Hispanic" row). The African ancestry in group (2) was also wide ranging with a mode closer to 1/4th; 1.8% of Hispanics had majority-ancestry from the African ancestry component, yet many more had substantial African ancestry (SI Figure 1).
3
Supplemental Figure 1. Distribution of genetic ancestry in all self-reported ethnicity groups. Highlighted violin plots indicate the "expected" genetic ancestry for the given self-reported ethnicity. Each violin plot includes only those with ≥1/32 of the given genetic ancestry, with the numbers indicating the proportion of the self-reported ethnicity plotted as well as the absolute number. Subpopulations with fewer than 100 individuals were not shown. Vertical lines within the violin plot indicate the 25th, 50th, and 75th percentiles of genetic ancestry. The "any" self-reported ethnicity includes the whole study cohort.
Supplemental Figure 2. Same as Figure 2 but excluding “Mixed or Other Caucasian” patients. Supplemental Figure 3. (a and c) Distribution of self-reported ethnicities among those with medium genetic ancestry (a) and high genetic ancestry (c). Hatching indicates secondary self-reported ethnicities. Colors are indicated in panel (c), where the text overlay specifies the ethnicity indicated by the leftmost bar. (b and d) Comparison of ancestry-specific carrier rates among those with medium genetic ancestry (b) and high genetic ancestry (d) based on whether they self-reported the associated ethnicity (x-axis) or not (y-axis). Each dot represents a combination of a disease and an ancestry (e.g., cystic fibrosis in Europeans). Disease-ancestry-self-reported ethnicity combinations with no observed carriers in this dataset are shown on the axes.
Supplemental Figure 4. Variant frequency distribution in those with low vs medium or high guideline-related genetic ancestry. For the 16 conditions with ethnicity-specific guidelines (separate panels), patients with low genetic ancestry (left of panel) and medium or high genetic ancestry (right of panel) carry pathogenic variants at different frequencies (y-axis). The genetic ancestry was chosen to correspond to the ethnicity with a guideline (e.g., Ashkenzi Jewish for Gaucher disease). Each horizontal line represents a variant, with a blue line indicating a variant observed in only one of the two subpopulations (e.g., in the low genetic ancestry subpopulation but not in the medium or high genetic ancestry subpopulation) and a black trace spanning the subpopulations indicating a single variant present in both subpopulations often at different frequencies (hence the upward or downward slope of middle segment). For most conditions, the medium-or-high-genetic ancestry subpopulation exhibited smaller variant diversity (i.e., fewer horizontal lines on right side of each panel) compared to the low-genetic ancestry subpopulation, as expected if founder variants are present.
Supplemental Table 1. Diseases included in the analysis.
Supplemental Table 2. Variants excluded in carrier rate analysis.
Supplemental Table 3. Self-reported ethnicities, genetic ancestries, and guideline recommendations as analyzed in this study.
Supplemental Table 4. Carriers missed by ethnicity-specific carrier screening compared to pan-ethnic expanded carrier screening. Individuals carriers for multiple diseases were counted for each disease.
Supplemental Table 5. Distributions of frequencies for variants observed in the low vs. medium/high
genetic ancestry groups.
Supplemental Figure 1
Supplemental Figure 2
Supplemental Figure 3
Supplemental Figure 4
Kaseniit et al. Supplemental Tables Table S1
Table S1: Diseases included in the analysisDisease Gene21-hydroxylase-deficient congenital adrenal hyperplasia CYP21A2ABCC8-related hyperinsulinism ABCC8alpha thalassemia HBA1alpha-mannosidosis MAN2B1alpha-sarcoglycanopathy SGCAAndermann syndrome SLC12A6ARSACS SACSaspartylglycosaminuria AGAataxia with vitamin E deficiency TTPAataxia-telangiectasia ATMBardet-Biedl syndrome, BBS1-related BBS1Bardet-Biedl syndrome, BBS10-related BBS10beta-sarcoglycanopathy SGCBbiotinidase deficiency BTDBloom syndrome BLMCanavan disease ASPAcarnitine palmitoyltransferase IA deficiency CPT1Acarnitine palmitoyltransferase II deficiency CPT2cartilage-hair hypoplasia RMRPcitrullinemia type 1 ASS1CLN3-related neuronal ceroid lipofuscinosis CLN3CLN5-related neuronal ceroid lipofuscinosis CLN5Cohen syndrome VPS13Bcongenital disorder of glycosylation type Ia PMM2congenital disorder of glycosylation type Ib MPIcongenital Finnish nephrosis NPHS1Costeff optic atrophy syndrome OPA3cystic fibrosis CFTRcystinosis CTNSD-bifunctional protein deficiency HSD17B4familial dysautonomia IKBKAPfamilial Mediterranean fever MEFVFanconi anemia type C FANCCFKTN-related disorders FKTNfragile X syndrome FMR1galactosemia GALTGaucher disease GBAGJB2-related DFNB1 nonsyndromic hearing loss and deafnessGJB2glutaric acidemia type 1 GCDHglycogen storage disease type Ia G6PCglycogen storage disease type Ib SLC37A4glycogen storage disease type III AGLGRACILE syndrome BCS1LHADHA-related Disorders HADHAHb beta chain-related hemoglobinopathy HBBhereditary fructose intolerance ALDOBHerlitz junctional epidermolysis bullosa, LAMA3-related LAMA3Herlitz junctional epidermolysis bullosa, LAMB3-related LAMB3Herlitz junctional epidermolysis bullosa, LAMC2-related LAMC2hexosaminidase A deficiency HEXA
Kaseniit et al. Supplemental Tables Table S1
Table S1: Diseases included in the analysisDisease Genehomocystinuria caused by cystathionine beta-synthase deficiencyCBShypophosphatasia, autosomal recessive ALPLinclusion body myopathy 2 GNEisovaleric acidemia IVDJoubert syndrome 2 TMEM216Krabbe disease GALClipoamide dehydrogenase deficiency DLDmaple syrup urine disease type 1B BCKDHBmedium chain acyl-CoA dehydrogenase deficiency ACADMmegalencephalic leukoencephalopathy with subcortical cystsMLC1metachromatic leukodystrophy ARSAmucolipidosis IV MCOLN1mucopolysaccharidosis type I IDUAmuscle-eye-brain disease POMGNT1NEB-related nemaline myopathy NEBNiemann-Pick disease type C NPC1Niemann-Pick disease, SMPD1-associated SMPD1Nijmegen breakage syndrome NBNNorthern epilepsy CLN8PCDH15-related disorders PCDH15Pendred syndrome SLC26A4PEX1-related Zellweger syndrome spectrum PEX1phenylalanine hydroxylase deficiency PAHPKHD1-related autosomal recessive polycystic kidney diseasePKHD1polyglandular autoimmune syndrome type 1 AIREPompe disease GAAPPT1-related neuronal ceroid lipofuscinosis PPT1primary carnitine deficiency SLC22A5primary hyperoxaluria type 1 AGXTprimary hyperoxaluria type 2 GRHPRPROP1-related combined pituitary hormone deficiency PROP1pycnodysostosis CTSKrhizomelic chondrodysplasia punctata type 1 PEX7Salla disease SLC17A5Segawa syndrome THSjogren-Larsson syndrome ALDH3A2Smith-Lemli-Opitz syndrome DHCR7spinal muscular atrophy SMN1steroid-resistant nephrotic syndrome NPHS2sulfate transporter-related osteochondrodysplasia SLC26A2TPP1-related neuronal ceroid lipofuscinosis TPP1tyrosinemia type I FAHUsher syndrome type 3 CLRN1very long chain acyl-CoA dehydrogenase deficiency ACADVLWilson disease ATP7BX-linked juvenile retinoschisis RS1
Kaseniit et al. Supplemental Tables Table S2
Table S2: Variants excluded in carrier rate analysisNM_000500.7(CYP21A2):c.955C>T(Q319*) with duplicationNM_000060.2(BTD):c.1330G>C(D444H)NM_000277.1(PAH):c.688G>A(V230I)NM_014625.2(NPHS2):c.686G>A(R229Q)NM_004004.5(GJB2):c.101T>C(M34T)NM_002225.3(IVD):c.941C>T(A314V, aka A311V)NM_000492.3(CFTR):c.1210-7_1210-6delTT(aka IVS8-5T)
Kas
eniit
et a
l. S
uppl
emen
tal T
able
sTa
ble
S3
Tabl
e S3
: Sel
f-rep
orte
d et
hnic
ities
, gen
etic
anc
estr
ies,
and
gui
delin
e re
com
men
datio
ns a
s an
alyz
ed in
this
stu
dy.
Self-
repo
rted
eth
nici
ty o
n re
quis
ition
form
Self-
repo
rted
eth
nici
ty
used
in s
tudy
Rel
ated
/exp
ecte
d ge
netic
an
cest
ryA
CM
G te
rm (b
ased
on
Edw
ards
et a
l. O
bste
tric
s &
Gyn
ecol
ogy
2015
)A
CO
G te
rm (b
ased
on
com
mitt
e op
inio
n 69
1)
Gui
delin
e re
com
men
datio
ns a
s an
alyz
ed in
man
uscr
ipt (
in a
dditi
on to
pa
n-et
hnic
cys
tic fi
bros
is a
nd s
pina
l m
uscu
lar a
trop
hy s
cree
ning
)
Anc
estr
y-ba
sed
guid
elin
es a
s an
alyz
ed
in m
anus
crip
t (in
add
ition
to c
ystic
fib
rosi
s an
d sp
inal
mus
cula
r atr
ophy
sc
reen
ing)
Afri
can
or A
frica
n-A
mer
ican
Afri
can
or A
frica
n-A
mer
ican
Afri
can
Afri
can
Am
eric
ans
(rec
omm
enda
tion
for
hem
oglo
bino
path
ies
scre
enin
g)A
frica
n de
scen
t (re
com
men
datio
n fo
r he
mog
lobi
nopa
thie
s sc
reen
ing)
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
self-
repo
rting
as
Afri
can
or A
frica
n-A
mer
ican
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
with
med
ium
or h
ighe
r lev
els
of
Afri
can
GA
Ash
kena
zi J
ewis
hA
shke
nazi
Jew
ish
Ash
kena
zi J
ewis
hA
shke
nazi
Jew
ish
(rec
omm
enda
tion
for
vario
us d
isea
ses)
Ash
kena
zi J
ewis
h de
scen
t (r
ecom
men
datio
n fo
r var
ious
dis
ease
s)
For t
hose
sel
f-rep
ortin
g as
Ash
kena
zi
Jew
ish,
scr
eeni
ng fo
r: - h
exos
amin
idas
e A
de
ficie
ncy
- Can
avan
dis
ease
- fa
mili
al
dysa
uton
omia
- B
loom
syn
drom
e -
Gau
cher
dis
ease
- Fa
ncon
i ane
mia
type
C
- muc
olip
idos
is IV
- N
iem
ann-
Pic
k di
seas
e, S
MP
D1-
asso
ciat
ed -
AB
CC
8-re
late
d hy
perin
sulin
ism
- gl
ycog
en s
tora
ge
dise
ase
type
Ia -
Joub
ert s
yndr
ome
2 -
map
le s
yrup
urin
e di
seas
e ty
pe 1
B -
Ush
er s
yndr
ome
type
3 -
PC
DH
15-r
elat
ed
diso
rder
s
For t
hose
with
med
ium
or h
ighe
r lev
els
of
Ash
kena
zi J
ewis
h, s
cree
ning
for:
- he
xosa
min
idas
e A
def
icie
ncy
- Can
avan
di
seas
e - f
amili
al d
ysau
tono
mia
- B
loom
sy
ndro
me
- Gau
cher
dis
ease
- Fa
ncon
i an
emia
type
C -
muc
olip
idos
is IV
- N
iem
ann-
Pic
k di
seas
e, S
MP
D1-
asso
ciat
ed -
AB
CC
8-re
late
d hy
perin
sulin
ism
- gl
ycog
en s
tora
ge
dise
ase
type
Ia -
Joub
ert s
yndr
ome
2 -
map
le s
yrup
urin
e di
seas
e ty
pe 1
B -
Ush
er s
yndr
ome
type
3 -
PC
DH
15-r
elat
ed
diso
rder
s
His
pani
cH
ispa
nic
Nat
ive
Am
eric
an, E
urop
ean
N/A
His
pani
c de
scen
t (no
eth
nici
ty-s
peci
fic
reco
mm
enda
tion;
men
tions
that
po
pula
tion
has
incr
ease
d be
ta-
thal
asse
mia
car
rier r
ate)
Non
eN
one
Mid
dle
Eas
tern
Mid
dle
Eas
tern
Mid
dle
Eas
tern
N/A
Mid
dle
Eas
tern
des
cent
(rec
omm
enda
tion
for h
emog
lobi
nopa
thie
s sc
reen
ing)
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
self-
repo
rting
as
Mid
dle
Eas
tern
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
with
med
ium
or h
ighe
r lev
els
of
Mid
dle
Eas
tern
GA
Nor
ther
n E
urop
ean
Nor
ther
n E
urop
ean
Eur
opea
nN
/AN
/AN
one
Non
e
Sou
ther
n E
urop
ean
Sou
ther
n E
urop
ean
Eur
opea
nM
edite
rran
ean
(rec
omm
enda
tion
for
hem
oglo
bino
path
ies
scre
enin
g)M
edite
rran
ean
desc
ent (
reco
mm
enda
tion
for h
emog
lobi
nopa
thie
s sc
reen
ing)
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
self-
repo
rting
as
Sou
ther
n E
urop
ean
Non
e
Sou
th A
sian
Sou
th A
sian
Sou
th A
sian
N/A
N/A
Non
e
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
with
med
ium
or h
ighe
r lev
els
of
Sou
th A
sian
GA
Sou
thea
st A
sian
Sou
thea
st A
sian
Sou
th A
sian
, Eas
t Asi
anS
outh
east
Asi
an (r
ecom
men
datio
n fo
r he
mog
lobi
nopa
thie
s sc
reen
ing)
Sou
thea
st A
sian
des
cent
(r
ecom
men
datio
n fo
r hem
oglo
bino
path
ies
scre
enin
g)
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
self-
repo
rting
as
Sou
thea
st A
sian
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
with
med
ium
or h
ighe
r lev
els
of
Sou
th A
sian
GA
or E
ast A
sian
GA
Eas
t Asi
anE
ast A
sian
Eas
t Asi
anN
/AN
/AN
one
alph
a th
alas
sem
ia a
nd H
b be
ta c
hain
-re
late
d he
mog
lobi
nopa
thy
scre
enin
g fo
r th
ose
with
med
ium
or h
ighe
r lev
els
of E
ast
Asi
an G
A
N/A
Not
incl
uded
in s
tudy
N/A
N/A
Wes
t Ind
ian
desc
ent (
reco
mm
enda
tion
for
hem
oglo
bino
path
ies
scre
enin
g)N
/AN
/AM
ixed
or O
ther
Cau
casi
anM
ixed
or O
ther
Cau
casi
anN
/AN
/AN
/AN
/AN
/A
Fren
ch C
anad
ian
or C
ajun
Not
incl
uded
in s
tudy
N/A
Fren
ch-C
anad
ian
or C
ajun
des
cent
(r
ecom
men
datio
n fo
r Tay
-Sac
hs
scre
enin
g)
Fren
ch-C
anad
ian
or C
ajun
des
cent
(r
ecom
men
datio
n fo
r Tay
-Sac
hs
scre
enin
g)N
/AN
/AFi
nnis
hN
ot in
clud
ed in
stu
dyN
/AN
/AN
/AN
/AN
/AN
ativ
e A
mer
ican
Not
incl
uded
in s
tudy
N/A
N/A
N/A
N/A
N/A
Pac
ific
Isla
nder
Not
incl
uded
in s
tudy
N/A
N/A
N/A
N/A
N/A
Unk
now
nN
ot in
clud
ed in
stu
dyN
/AN
/AN
/AN
/AN
/A
Kas
eniit
et a
l. S
uppl
emen
tal T
able
sTa
ble
S4
Tabl
e S4
: Car
riers
mis
sed
by e
thni
city
-spe
cific
car
rier s
cree
ning
com
pare
d to
pan
-eth
nic
expa
nded
car
rier s
cree
ning
. Ind
ivid
uals
who
wer
e ca
rrie
rs fo
r m
ultip
le d
isea
ses
wer
e co
unte
d fo
r eac
h di
seas
e.
ethn
icity
carr
iers
id
entif
ied
carr
iers
m
isse
dpa
tient
s te
sted
carr
ier s
ensi
tivity
re
lativ
e to
pan
-et
hnic
EC
Sm
isse
d ca
rrie
rs re
lativ
e to
pan
-eth
nic
ECS
dise
ases
with
m
isse
d ca
rrie
rsto
p di
seas
es w
ith p
ropo
rtio
n of
all
mis
sed
carr
iers
Afri
can
or A
frica
n-A
mer
ican
2080
985
6996
67.9
0%32
.10%
87
21-h
ydro
xyla
se-d
efic
ient
con
geni
tal a
dren
al h
yper
plas
ia (8
.9%
) fr
agile
X s
yndr
ome
(8.5
%)
GJB
2-re
late
d D
FNB
1 no
nsyn
drom
ic h
earin
g lo
ss a
nd d
eafn
ess
(5.5
%)
Pom
pe d
isea
se (3
.6%
) g
alac
tose
mia
(3.1
%)
phe
nyla
lani
ne h
ydro
xyla
se d
efic
ienc
y (2
.6%
) c
onge
nita
l dis
orde
r of g
lyco
syla
tion
type
Ia (2
.5%
) g
luta
ric a
cide
mia
type
1 (2
.4%
) fa
mili
al M
edite
rran
ean
feve
r (2.
2%)
med
ium
cha
in a
cyl-C
oA d
ehyd
roge
nase
def
icie
ncy
(2.2
%)
Ash
kena
zi J
ewis
h28
2451
5296
8735
.40%
64.6
0%74
fam
ilial
Med
iterr
anea
n fe
ver (
19.2
%)
21-
hydr
oxyl
ase-
defic
ient
con
geni
tal a
dren
al h
yper
plas
ia (1
6.9%
) G
JB2-
rela
ted
DFN
B1
nons
yndr
omic
hea
ring
loss
and
dea
fnes
s (8
.6%
) p
heny
lala
nine
hyd
roxy
lase
def
icie
ncy
(6.5
%)
alp
ha th
alas
sem
ia (6
.2%
) c
arni
tine
palm
itoyl
trans
fera
se II
def
icie
ncy
(4.1
%)
Wils
on d
isea
se (4
.0%
) fr
agile
X s
yndr
ome
(3.8
%)
Sm
ith-L
emli-
Opi
tz s
yndr
ome
(3.7
%)
PK
HD
1-re
late
d au
toso
mal
rece
ssiv
e po
lycy
stic
kid
ney
dise
ase
(3.1
%)
Eas
t Asi
an14
924
3367
875.
80%
94.2
0%92
GJB
2-re
late
d D
FNB
1 no
nsyn
drom
ic h
earin
g lo
ss a
nd d
eafn
ess
(33.
5%)
alp
ha th
alas
sem
ia (8
.9%
) K
rabb
e di
seas
e (5
.2%
) P
endr
ed s
yndr
ome
(5.0
%)
Hb
beta
cha
in-r
elat
ed h
emog
lobi
nopa
thy
(4.4
%)
Wils
on d
isea
se (3
.7%
) 2
1-hy
drox
ylas
e-de
ficie
nt c
onge
nita
l adr
enal
hyp
erpl
asia
(3.2
%)
prim
ary
carn
itine
def
icie
ncy
(3.1
%)
phe
nyla
lani
ne h
ydro
xyla
se d
efic
ienc
y (2
.5%
) fr
agile
X s
yndr
ome
(2.3
%)
Kas
eniit
et a
l. S
uppl
emen
tal T
able
sTa
ble
S4
Tabl
e S4
: Car
riers
mis
sed
by e
thni
city
-spe
cific
car
rier s
cree
ning
com
pare
d to
pan
-eth
nic
expa
nded
car
rier s
cree
ning
. Ind
ivid
uals
who
wer
e ca
rrie
rs fo
r m
ultip
le d
isea
ses
wer
e co
unte
d fo
r eac
h di
seas
e.
ethn
icity
carr
iers
id
entif
ied
carr
iers
m
isse
dpa
tient
s te
sted
carr
ier s
ensi
tivity
re
lativ
e to
pan
-et
hnic
EC
Sm
isse
d ca
rrie
rs re
lativ
e to
pan
-eth
nic
ECS
dise
ases
with
m
isse
d ca
rrie
rsto
p di
seas
es w
ith p
ropo
rtio
n of
all
mis
sed
carr
iers
His
pani
c28
619
0666
9013
.00%
87.0
0%87
21-h
ydro
xyla
se-d
efic
ient
con
geni
tal a
dren
al h
yper
plas
ia (1
4.0%
) a
lpha
thal
asse
mia
(10.
4%)
GJB
2-re
late
d D
FNB
1 no
nsyn
drom
ic h
earin
g lo
ss a
nd d
eafn
ess
(9.2
%)
frag
ile X
syn
drom
e (5
.8%
) fa
mili
al M
edite
rran
ean
feve
r (5.
0%)
Hb
beta
cha
in-r
elat
ed h
emog
lobi
nopa
thy
(4.7
%)
phe
nyla
lani
ne h
ydro
xyla
se d
efic
ienc
y (3
.7%
) P
KH
D1-
rela
ted
auto
som
al re
cess
ive
poly
cyst
ic k
idne
y di
seas
e (3
.1%
) c
onge
nita
l dis
orde
r of g
lyco
syla
tion
type
Ia (3
.0%
) S
mith
-Lem
li-O
pitz
syn
drom
e (2
.7%
)
Mid
dle
Eas
tern
281
671
2152
29.5
0%70
.50%
69
fam
ilial
Med
iterr
anea
n fe
ver (
22.5
%)
21-
hydr
oxyl
ase-
defic
ient
con
geni
tal a
dren
al h
yper
plas
ia (1
3.1%
) fr
agile
X s
yndr
ome
(8.3
%)
GJB
2-re
late
d D
FNB
1 no
nsyn
drom
ic h
earin
g lo
ss a
nd d
eafn
ess
(7.2
%)
phe
nyla
lani
ne h
ydro
xyla
se d
efic
ienc
y (6
.6%
) P
KH
D1-
rela
ted
auto
som
al re
cess
ive
poly
cyst
ic k
idne
y di
seas
e (3
.4%
) P
ompe
dis
ease
(2.8
%)
her
edita
ry fr
ucto
se in
tole
ranc
e (2
.7%
) W
ilson
dis
ease
(2.4
%)
incl
usio
n bo
dy m
yopa
thy
2 (2
.2%
)
Mix
ed o
r Oth
er
Cau
casi
an18
2510
585
2863
914
.70%
85.3
0%93
21-h
ydro
xyla
se-d
efic
ient
con
geni
tal a
dren
al h
yper
plas
ia (7
.1%
) G
JB2-
rela
ted
DFN
B1
nons
yndr
omic
hea
ring
loss
and
dea
fnes
s (7
.1%
) fa
mili
al M
edite
rran
ean
feve
r (5.
8%)
frag
ile X
syn
drom
e (5
.2%
) p
heny
lala
nine
hyd
roxy
lase
def
icie
ncy
(5.1
%)
Sm
ith-L
emli-
Opi
tz s
yndr
ome
(4.3
%)
med
ium
cha
in a
cyl-C
oA d
ehyd
roge
nase
def
icie
ncy
(3.7
%)
alp
ha th
alas
sem
ia (3
.3%
) P
ompe
dis
ease
(3.1
%)
con
geni
tal d
isor
der o
f gly
cosy
latio
n ty
pe Ia
(2.8
%)
Kas
eniit
et a
l. S
uppl
emen
tal T
able
sTa
ble
S4
Tabl
e S4
: Car
riers
mis
sed
by e
thni
city
-spe
cific
car
rier s
cree
ning
com
pare
d to
pan
-eth
nic
expa
nded
car
rier s
cree
ning
. Ind
ivid
uals
who
wer
e ca
rrie
rs fo
r m
ultip
le d
isea
ses
wer
e co
unte
d fo
r eac
h di
seas
e.
ethn
icity
carr
iers
id
entif
ied
carr
iers
m
isse
dpa
tient
s te
sted
carr
ier s
ensi
tivity
re
lativ
e to
pan
-et
hnic
EC
Sm
isse
d ca
rrie
rs re
lativ
e to
pan
-eth
nic
ECS
dise
ases
with
m
isse
d ca
rrie
rsto
p di
seas
es w
ith p
ropo
rtio
n of
all
mis
sed
carr
iers
Nor
ther
n E
urop
ean
1495
8110
2131
715
.60%
84.4
0%93
21-h
ydro
xyla
se-d
efic
ient
con
geni
tal a
dren
al h
yper
plas
ia (7
.1%
) G
JB2-
rela
ted
DFN
B1
nons
yndr
omic
hea
ring
loss
and
dea
fnes
s (6
.5%
) p
heny
lala
nine
hyd
roxy
lase
def
icie
ncy
(5.3
%)
frag
ile X
syn
drom
e (5
.1%
) fa
mili
al M
edite
rran
ean
feve
r (5.
0%)
Sm
ith-L
emli-
Opi
tz s
yndr
ome
(4.2
%)
con
geni
tal d
isor
der o
f gly
cosy
latio
n ty
pe Ia
(3.5
%)
med
ium
cha
in a
cyl-C
oA d
ehyd
roge
nase
def
icie
ncy
(3.5
%)
Pom
pe d
isea
se (3
.0%
) P
endr
ed s
yndr
ome
(2.4
%)
Sou
th A
sian
189
1100
4433
14.7
0%85
.30%
80
alph
a th
alas
sem
ia (2
3.3%
) H
b be
ta c
hain
-rel
ated
hem
oglo
bino
path
y (1
2.5%
) G
JB2-
rela
ted
DFN
B1
nons
yndr
omic
hea
ring
loss
and
dea
fnes
s (9
.8%
) 2
1-hy
drox
ylas
e-de
ficie
nt c
onge
nita
l adr
enal
hyp
erpl
asia
(5.5
%)
frag
ile X
syn
drom
e (4
.2%
) fa
mili
al M
edite
rran
ean
feve
r (3.
6%)
Wils
on d
isea
se (3
.4%
) P
endr
ed s
yndr
ome
(3.1
%)
prim
ary
carn
itine
def
icie
ncy
(3.0
%)
med
ium
cha
in a
cyl-C
oA d
ehyd
roge
nase
def
icie
ncy
(1.8
%)
Sou
thea
st A
sian
229
524
1882
30.4
0%69
.60%
69
GJB
2-re
late
d D
FNB
1 no
nsyn
drom
ic h
earin
g lo
ss a
nd d
eafn
ess
(49.
4%)
Pen
dred
syn
drom
e (5
.0%
) K
rabb
e di
seas
e (3
.8%
) p
rimar
y ca
rniti
ne d
efic
ienc
y (3
.8%
) 2
1-hy
drox
ylas
e-de
ficie
nt c
onge
nita
l adr
enal
hyp
erpl
asia
(3.4
%)
pol
ygla
ndul
ar a
utoi
mm
une
synd
rom
e ty
pe 1
(2.5
%)
frag
ile X
syn
drom
e (2
.1%
) p
heny
lala
nine
hyd
roxy
lase
def
icie
ncy
(2.1
%)
Wils
on d
isea
se (1
.7%
) P
ompe
dis
ease
(1.5
%)
Kas
eniit
et a
l. S
uppl
emen
tal T
able
sTa
ble
S4
Tabl
e S4
: Car
riers
mis
sed
by e
thni
city
-spe
cific
car
rier s
cree
ning
com
pare
d to
pan
-eth
nic
expa
nded
car
rier s
cree
ning
. Ind
ivid
uals
who
wer
e ca
rrie
rs fo
r m
ultip
le d
isea
ses
wer
e co
unte
d fo
r eac
h di
seas
e.
ethn
icity
carr
iers
id
entif
ied
carr
iers
m
isse
dpa
tient
s te
sted
carr
ier s
ensi
tivity
re
lativ
e to
pan
-et
hnic
EC
Sm
isse
d ca
rrie
rs re
lativ
e to
pan
-eth
nic
ECS
dise
ases
with
m
isse
d ca
rrie
rsto
p di
seas
es w
ith p
ropo
rtio
n of
all
mis
sed
carr
iers
Sou
ther
n E
urop
ean
295
990
2812
23.0
0%77
.00%
84
fam
ilial
Med
iterr
anea
n fe
ver (
10.2
%)
21-
hydr
oxyl
ase-
defic
ient
con
geni
tal a
dren
al h
yper
plas
ia (1
0.0%
) G
JB2-
rela
ted
DFN
B1
nons
yndr
omic
hea
ring
loss
and
dea
fnes
s (7
.8%
) p
heny
lala
nine
hyd
roxy
lase
def
icie
ncy
(6.8
%)
frag
ile X
syn
drom
e (6
.2%
) S
mith
-Lem
li-O
pitz
syn
drom
e (4
.1%
) P
ompe
dis
ease
(3.6
%)
her
edita
ry fr
ucto
se in
tole
ranc
e (3
.5%
) c
onge
nita
l dis
orde
r of g
lyco
syla
tion
type
Ia (3
.2%
) W
ilson
dis
ease
(2.3
%)
all
9653
3245
691
395
22.9
0%77
.10%
94
GJB
2-re
late
d D
FNB
1 no
nsyn
drom
ic h
earin
g lo
ss a
nd d
eafn
ess
(10.
0%)
21-
hydr
oxyl
ase-
defic
ient
con
geni
tal a
dren
al h
yper
plas
ia (8
.9%
) fa
mili
al M
edite
rran
ean
feve
r (7.
6%)
phe
nyla
lani
ne h
ydro
xyla
se d
efic
ienc
y (4
.9%
) fr
agile
X s
yndr
ome
(4.9
%)
alp
ha th
alas
sem
ia (4
.6%
) S
mith
-Lem
li-O
pitz
syn
drom
e (3
.5%
) W
ilson
dis
ease
(2.7
%)
con
geni
tal d
isor
der o
f gly
cosy
latio
n ty
pe Ia
(2.6
%)
Pom
pe d
isea
se (2
.6%
)
Table S5 is included as a supplemental Excel file on the GIM website.
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