Science - USA (2022-04-29)

trait) were enriched for SNPs associated in
any of the 119 behavioral GWASs (fig. S31).
Only one GWAS (Q66,“lifts leg to urinate”)
was significant [adjustedpvalue (padj) = 0.013].
Thus, although spurious associations due to
aesthetic traits are a concern in multibreed

GWASs, they are likely rare in the GWAS run

on our diverse cohort.

Unattributed heritability

A large proportion of the genetic and envi-

ronmental contributions to behavior remains

undiscovered. The SNPs that we found to be

associated with heritable (h^2 SNP> 0.1) behav-

ioral traits account for a smaller proportion

of overall heritability than do aesthetic trait

associations ( 22 ), consistent with a complex

genetic architecture. For the 14 physical traits,

Morrillet al.,Science 376 , eabk0639 (2022) 29 April 2022 10 of 15

Fig. 6. Genetics of aesthetic and
behavioral traits in dogs and
influence of breed ancestry in
mutts.(AtoC) In highly admixed
dogs with no breed ancestry over
45%, the fixed effects of breed ancestry
on (A) physical traits, (B) behavioral
factor scores, and (C) individual
behavioral question scores are shown.
(D) Manhattan plot for the GWAS of
surveyed height (Q121) from 1951 dogs,
including covariates for age and sex.
Linkage blocks (r^2 > 0.2) associated
(p<5×10−^8 ) with stature align
with previous associations for body
size in (a)IGF1R( 68 ), (b)LCORL( 40 ),
(c)GHR( 69 ), (d)SMAD2( 84 ),
(e)HMGA2( 69 ) and the nearby
(f)MSRB3, (g) a chromosome 12
retrogene insertion ofFGF4( 70 ),
(h)IGF1( 64 – 66 ), (i) anotherFGF4
retrogene on chromosome 18 ( 67 ),
(j)MED13L( 40 ), and (k)IGF2BP2( 40 ).
Two previously unknown associations
were found spanningJADE2andSAR1B,
and inANAPC1.(E) Random forest
models based on size-associated
SNPs (p<1×10−^5 ) accurately predict
body size and correlate strongly
(N= 310 dogs;Rpearson= 0.91,
p=8.8×10−^117 ,t= 37.451, df = 308)
with real measurements in those
dogs. (FtoH) Regional association
plots for (F) scores on Q36“gets stuck
behind objects,”(G) human sociability,
and (H) frequency of howling from
Q17. In addition to protein coding
genes (black boxes), we also show
representative open chromatin regions
(rOCRs; narrow vertical lines). We
annotated rOCRs genome-wide using
ENCODE methods ( 101 ) applied to
canine ATAC-seq (assay for transposase-
accessible chromatin using sequencing)
data from 14 tissues ( 102 ) and mam-
malian sequence constraint ( 103 ).
(I) Breeds show high genetic differenti-
ation, measured as the population
branch statistic, overlapping physical
trait associated loci compared with
~100,000 randomly permuted regions
(N= 1232, meanz= 0.49,p= 7.3 ×
10 −^33 ). Regions associated with behav-
ioral factors (N= 512, meanz= 0.03,
p= 0.224) and question scores (N= 9317, meanz= 0.00,p= 0.603) do not show such differentiation in breeds. Red circles indicate mean, with horizontal lines at the 25%
quartile, median, and 75% quartile. The shaded area is the probability density, with significant differentiation in red. ns, not significant; ****p< 0.0001 (Student’sttest).

ns ns ****

−2

0

2

4

behavior

factor

behavior

question

physical

trait

z

rOCRs

0.0

2.5

5.0

7.5

10.0

48.47 48.49 48.51

-log10(p-value)

FGF19 ORAOV1 CCND1

10.10 10.20 10.30 10.40

SLC38 SCN3A

chr18: 48,487,378

(G>A)

chr36: 10,238,073

(A>C)

genes

19.3 19.4 19.4 19.4 19.5

STAM HACD1 ST8SIA6

chr2: 19,430,669

(G>T)

CPPED1

0.0

2.5

5.0

7.5

10.0

30.1 30.2 30.3 30.4

-log10(p-value)

rOCRs

genes

chr6: 30,299,660

(C>T)

SNX29

Q36: “Gets stuck behind objects” Factor 1: Human sociability.

r^2 [0.0,0.2] (0.2,0.4] (0.4,0.6] (0.6,0.8] (0.8,1]

0

10

20

123 4 5 6 7 8 9 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38

-log

10

(p)

FGF4

retrogene

i

FGF4

retrogene

g

IGF1h

JADE2,

SAR1B

HMGA2e

MSRB3f

GHR SMAD2d

IGF1R, c

PGPEP1L

a

LCORLb

MED13Lj IGF2BP2

k

ANAPC1

p=5e-8

p=1e-6

1

2

3

20 40 60 80

measured height (cm)

predicted relative

height score

R=0.91; p=8.8x10-117

−5 0 5

LMER t-value

-10 10

shar pei

#3: Toy−direc.

Motor patternstoy-directed not toy-directed

am pit bull terr

aus shep

pinscherminiboston terr

#2: Arousal vizsla

level aroused composed

border collieaus cattle dog chihuahua beagle

#4: Biddability

biddable independent

#8: Proximity saint bernard malamute

seeking affectionate aloof

malamute

cocker spaniel

border collie

bull terr

chihuahua

dachshund

great dane german shep

greyhound

jack russ terr

maltese labrador ret

mastiff

mini pinscher

rhod ridge rottweiler

sheltie

shih tzu

toy siberian husky

poodle

yorkshire terr

#121 Size

ankle-high hip high

malamute

cocker spaniel aus cattle dog

beagle bichon frise

bloodhound

boston terr chihuahua chow chow

dachshund es spaniel

german

shep

labrador ret golden ret jack russ terr

lhasa apso

corgi

pomeranian

toy poodle rhod ridge siberian husky

vizsla

pt griffon

#125: Ear

shapedropped pricked

-10 −5−5 0 55

A Physical traits

B Factors

−5 0 5

LMER t-value

chihuahua labrador ret

#60: Avoids

getting wet agree disagree

chihuahua toy poodlegolden ret

#97: Shakes

occasionally agree disagree

beagle

bloodhound

#17: Howlsnever always

chow chow

#54:

Retrievesagree disagree

-10 −5 5

C Behavior questions

D

E

H

I

Q17: “Howls”

F G

RESEARCH | RESEARCH ARTICLE