Genetics of Language

Genetics of Language & Language
Disorders
Karin Stromswold*
Dept. of Psychology & Center for Cognitive Science
Rutgers University - New Brunswick
Portions of this work were supported by
• Johnson & Johnson Foundation
• John Merck Foundation
• Charles & Johanna Busch Biomedical Research Grant
• Bamford-Lahey Children’s Foundation
• National Science Foundation (BCS-9875168, BCS-0042561, BCS-0124095)
* Correspondence may be sent to [email protected]
Karin Stromswold (2002). Genetics of Language and Language Disorders
Key Questions
• Do genetic factors affect people’s ability to acquire and use
language?
• Do these factors affect 'normal' people’s linguistic abilities
or just those with language disorders?
• Do language-specific genes exist?
• Are genetic factors involved in all aspects of language?
• Are the same genetic factors involved in all aspects of
language?
• How do genes/environment interact?
Karin Stromswold (2002). Genetics of Language and Language Disorders
Innateness Hypothesis & Heritability
• Typical evidence: Universal, learnable, modular
• Genetic evidence: If innate cognitive predisposition or neural
structures enable us to use/acquire language, they must be encoded in
our DNA
• Why we might fail to find evidence for language heritability
Heritability = amount of individual variation due to genetic factors
– The Innateness Hypothesis is wrong
– Linguistically-speaking, (normal) people are genetically identical
Chomsky (1980): Language is like number of fingers
Lieberman (1984): Language is like height
Karin Stromswold (2002). Genetics of Language and Language Disorders
Innateness Hypothesis & Heritability
• Individual differences may exist
– Acquisition rate for vocabulary (e.g., Goldfield & Reznick, 1990),
morphology (e.g., deVilliers & deVilliers, 1973), syntax (e.g.,
Stromswold 1990, 1995, Snyder & Stromswold 1997).….
– Adult linguistic proficiency: verbal fluency (e.g., Day, 1979),
compound nouns (e.g., Gleitman & Gleitman, 1970), sentence
processing (e.g., Corely & Corley, 1995; Bever et al., 1989),
second language acquisition (e.g., Fillmore, 1979), grammaticality
judgments (e.g., Ross, 1979; Nagatu, 1992; Cowart, 1994).
• Caveat: Genetic factors could account for differences
among abnormal populations but not normal populations
– The case with number of fingers: genetic syndromes associated
with too many/few fingers
– (Contrast with heritability of finger length)
Karin Stromswold (2002). Genetics of Language and Language Disorders
Methodology
• The power of meta-analyses:
– Increase statistical power
– Methodological weaknesses of individual studies less worrisome
• Searched PsycINFO, ERIC, & Medline databases for
– language, linguistic, articul, speech, read or spell
AND
– hereditary, genetic, famil, twin, adoption, chromosom, linkage,
pedigree, sex-ratio, segregation, aggregation, DNA, or RNA
• Excluded language disorders that were acquired,
progressive, syndromic, or secondary to hearing loss,
mental retardation, psychiatric/neurological disorder etc.
Karin Stromswold (2002). Genetics of Language and Language Disorders
Family Aggregation of Spoken Disorders
• Do language disorders aggregate (cluster) in families?
• Yes: Meta-analyses of 18 studies revealed
– SLI probands are more likely to have a positive family history
46% (range 24-78%) vs. 18% (range 3-46%)
– SLI probands have more impaired relatives than do controls
28% (range 20-42%) vs. 9% (range 3-19%)
• Caveat: Difficult to separate the role of genes vs.
environment (Deviant Linguistic Environment Hypothesis)
Karin Stromswold (2002). Genetics of Language and Language Disorders
DLEH Predictions are not Borne Out
• Language impairments sometimes skip generations
• Most severely impaired children don’t come from families with
highest incidence of impairment
• Parents who speak normally (but have history of language delay) are
more likely to have language-impaired children
• Even in families with very high impairment rates, some family
members are normal
• In most families, some siblings are impaired and others are not
• No relationship between birth order and probability of impairment
• Concordance is no greater between primary care provider and child &
other first degree relatives
• Language-impaired children don’t always have the same impairment
as their relatives
Karin Stromswold (2002). Genetics of Language and Language Disorders
Pedigree Studies: Modes of Transmission
• Autosomal Dominant (AD): Most probands will have 1 impaired
parent, and half of siblings will be impaired
• Autosomal Recessive (AR): Most probands will have 2 unaffected
parents, and one quarter of siblings will be affected
• X-linked Recessive (XLR): Impaired males have 1 bad gene,
impaired females have two bad genes. Thus, the M:F is n:n2 (where n
is the frequency of the disordered allelle)
• Most genetic language disorders aren’t SML. Review of lit shows
– One-third of probands have 1 affected parent: Genetic heterogeneity or AD with
high rate of spontaneous mutation, or incomplete penetrance or expressivity
– One-quarter of probands have 2 affected parents: High assortative mating, very
high incidence of language disorders, SML models are wrong
– One-third of siblings are impaired: Either AR or genetically heterogeneous
– Sex ratios generally between 2:1 to 3:1. Even most extreme only 6:1 Not XLR
Karin Stromswold (2002). Genetics of Language and Language Disorders
Colorado Adoption Project (CAP)
• Rationale: If genes are important for a trait, adopted children’s abilities will
resemble their biological relatives’abilities. If environment is important, adopted
children will resemble their adopted relatives.
• Design: Large (N>300) longitudinal study that compares adopted and nonadopted
children’s skills with those of their biological and adopted parents and siblings.
• Language Disorders (Felsenfeld & Plomin, 1997): 156 children at age 7
– Positive biological family history was the best predictor of language disorders
– 25% of children with + biological family history were impaired (9% with + adopted FH)
• Sibling comparisons at age 7 (Cardon et al., 1992):
– Vocab + verbal fluency h = .90 (IQ-related = .46, Language-specific = .83)
– Fluency only h = .33 (IQ-related = .54, Language-specific = .20)
– Vocab only h = .47 (IQ-related = .69, Language-specific = .00)
Karin Stromswold (2002). Genetics of Language and Language Disorders
CAP Parent-Child Comparison (Plomin et al., 1997)
Verbal Abilities
Processing Speed
Spatial Abilities
Recognition Memory
Karin Stromswold (2002). Genetics of Language and Language Disorders
CAP Conclusions
• Heritable factors affect verbal abilities more than other types of
abilities
• The influence of genetic factors becomes more apparent with age
• Specific-to-language factors are only seen at age 7 (but this may be
because overall IQ was used).
• Caveats about adoption studies:
– All studies from a single group of children (what if not representative)
– Verbal assortative mating was greater for adoptive parents than biological
parents: This probably lowered heritability estimates
– Selective adoptive placement was not a problem (low correlation between
adoptive and biological mothers’ verbal skills)
Karin Stromswold (2002). Genetics of Language and Language Disorders
Twin Study Rationale
• Rationale: Identical (monozygotic, MZ) and non-identical
(dizygotic, DZ) twin pairs share the same environment, but
MZ cotwins share 100% of their DNA, whereas DZ twins
share 50% of their DNA
• Therefore: If MZ cotwins are more similar linguistically
than DZ twins, this suggests that genetics plays a role in
language.
• Can quantify the relative role of genetics and environment
by measuring how much more similar MZ twins are than
DZ twins.
Karin Stromswold (2002). Genetics of Language and Language Disorders
Concordance Rates for Twin Pairs
• Are concordance rates for MZ > DZ twins?
Number of Impaired Individuals in Concordant Pairs
Total Number of Impaired Individuals
• Two types of meta-analyses
– Mean rates: Treat each studies’ MZ & DZ concordance
rates as data points, and use sign- and t-tests to determine
if there is a significant difference.
– Overall rates: Pool data from all studies and calculate
overall concordance rates. Use Z-scores to test if MZ-DZ
rates are different
Karin Stromswold (2002). Genetics of Language and Language Disorders
Twin Correlational Analyses
• Are MZ twins’ test scores more highly correlated than DZ twins?
• Phenotypic variance = variation for a trait in a population
– Heritable factors: Falconer’s h2 = 2[rMZ - rDZ]
– Common environment factors: c2 = rMZ - h2
– Non-shared environmental factors: e2 = 1 - rMZ
• Unweighted meta-analysis: rMZ and rDZ are data points
• Weighted meta-analysis : Weighted mean Fisher’s z’s for MZ and
DZ twins were calculated and compared using Z-scores
[(N  3)z

z
 (N  3)
j
j
j
Z
zM Z  zDZ
1
1

NMZ  3 NDZ  3
Karin Stromswold (2002). Genetics of Language and Language Disorders
MZ Concordance Rates are Higher
• Spoken language disorders: 5 studies (266 MZ, 161 DZ pairs)
– Mean: 84% for MZ, 52% for DZ, p < .0001
– Overall: 84% for MZ, 48% for DZ, p < .0001
• Written language disorders: 5 studies (212 MZ, 199 DZ pairs)
– Mean: 76% for MZ, 41% for DZ, p < .01
– Overall: 75% for MZ, 43% for DZ, p < .0001
• Combined spoken/written disorders (478 MZ, 360 DZ pairs) :
– Mean: 80% for MZ, 46% for DZ, p < .0001
– Overall: 80% for MZ, 46% for DZ, p < .0001
• But why aren’t MZ concordance rates 100%? Three possibilities:
–
–
–
–
MZ twins aren’t identical genetically and/or environmentally
Expressivity of language disorders is incomplete
Failure to diagnose language disorders in some MZ cotwins
[DZ pair-wise concordance rate (26%) is similar to non-twin siblings (30%)]
Karin Stromswold (2002). Genetics of Language and Language Disorders
Spoken Language Disorders
Study
Bishop et al. (1995)
Dale et al. (1998)
Lewis & Thompson (1992)
Tomblin & Buckwalter (1994)
Tomblin & Buckwalter (1998)
Mean†
Overall†
Twin Pairs
63 MZ (52 M, 11 F)
27 DZ (20 M, 7 F)
75 MZ (sex N/A)
60 DZ (sex N/A
32 MZ† (24 M, 8 F)
25 DZ† (18 M, 7 F)
Diagnosis
SLI (by test scores)
56 MZ (sex N/A)
26 DZ (sex N/A)
40 MZ (sex N/A)
23 DZ (sex N/A)
SLI (questionnaire to speech
pathologists)
Poor composite language score (>1 SD
below mean)
TEDS twins with small vocabulary at
age 2 (bottom 5%)
Received speech or language therapy
Proband C oncordance
Strict criteria m z = 70%; dz = 46%*
Broad criteria m z = 94%; dz = 62%**
m z = 81%; dz = 42%****
Any disorder m z = 86%; dz = 48%**
Articulaton m z = 98%; dz = 36%****
LD m z = 70%; dz = 50%
Speech delay m z = 83%; dz = 0%*
m z = 89% MZ vs. 55% DZ**
m z = 96%; dz = 69% **
x mz = 84.4%; x dz = 52.1****
m z = 83.7%; dz = 48.3%****
263 MZ, 154 DZ
All significance lev els are f or one-tailed tests * p < .05; ** p < .01; *** p < .001, **** p < .0001
LD = Learning Disorder, SLI = Specif ic Language Impairment
† Overall and mean rates include Lewis & Thompson's "any diagnosis" data and Bishop et al.’s (1995) strict criteria data.
Karin Stromswold (2002). Genetics of Language and Language Disorders
Written Language Disorders
Study
Bakwin (1973)
Number of twin pairs
31 MZ (19 M, 12 F)
31 DZ (19 M, 12 F)
Diagnosis
Dyslexia
DeFries & Gillis (1993)
133 MZ (58 M, 75 F)
98 DZ (57 M, 41 F)
17 MZ (sex N/A)
10 DZ (sex N/A)
18 MZ (sex N/A)†
30 DZ (sex N/A) †
Dyslexia (PIAT scores )
Matheny et al. (1976)
Stevenson et al (1987)
Zerbin-Rubin (1967)
Mean
Overall††
17 MZ (sex N/A)
33 DZ (sex N/A)
Dyslexia or problems
with written language
Reading & spelling
retardation (Neale &
Schonell tests)
W ord blindness
212 MZ, 199 DZ
Proband C oncordance
Overall m z = 91%; dz = 45%***
Male m z = 91%; dz = 59%*
Female m z = 91%; dz = 15%****
m z = 68%; dz = 43%***
m z = 87%; dz = 33%**
Neale read m z = 33%; dz = 29%
Schon read m z = 35%; dz = 31%
Spelling m z = 50%; dz = 33%
m z = 100%; dz = 50%***
x mz = 76.2%; x dz = 40.6**
m z = 74.9%; dz = 42.7% DZ****
All significance lev els are for one-tailed tests * p < .05; ** p < .01; *** p < .001, **** p < .0001.
† Number of twin pairs varied according to diagnosis.
†† Mean and overall rates include Stev enson et al.'s "Schonell reading retarded" data
PIAT = Peabody Individual Achiv ement Test f or Word Recognition
Karin Stromswold (2002). Genetics of Language and Language Disorders
SLI Twins’ Test Performance
• Bishop et al (1995): 63 MZ, 27 DZ twin pairs
–
–
–
–
–
Articulation: Falconer’s h2 = 1.82
Phonological STM: DF h2g = 1.25
Receptive vocabulary: DF h2g = 1.35
Morphosyntax: Wechsler h2g = 1.10, CELF h2g = .56, TROG h2g = 1.09
(But when nonverbal IQ partialled out, no significant genetic effects)
• Bishop et al (1999):
– 27 MZ, 21 DZ: Pure tone sequence repetition DF h2g = .11
– 25 MZ, 22 DZ: Nonword repetition DF h2g = 1.17
• Tomblin & Buckwalter’s (1998) data minus triplets (58 twins):
– Falconer’s h2 = .66, p = .05
– Bivariate heritability for nonverbal IQ & language = .21
– Genetic correlation, RG = .01 (ie., different genetic factors influence verbal &
nonverbal disability)
Karin Stromswold (2002). Genetics of Language and Language Disorders
TEDS Twins’ Test Performance
• TEDS study: Large population-based, parent report twin study
• Dale et al (1998): Analyzed data for twins with the smallest vocabularies (bottom
5%tile, 135 twin pairs). DF h2g = .73 (vs. h2 = .25 for all TEDS twins)
• Eley et al. (1999): DF h2g greater for TED twins with small vocabularies than twins
with normal vocabularies.
• Eley et al. (2001): genetic continuity is greater for small vocab probands than other
proband groups
• Purcell et al. (2001): Are the genetic factors specific to vocabulary?
– When probands were selected based on small vocabularies, RG for low verbal &
nonverbal scores = 1.0 (i.e., the genetic factors that cause 2 years olds to have small
vocabularies are the same as those that cause them to have nonverbal delays.)
– When probands were selected based on poor nonverbal scores, the vocabulary-nonverbal
RG = .36
– [Why the asymmetry: Differences in homogeneity of the samples? Problems with the
measure? Directionality of effect?]
Karin Stromswold (2002). Genetics of Language and Language Disorders
Colorado Twin Study of Reading Disability
• Olson et al (1989): Genetic factors played a large role for phonological reading
(DF h2g = .93) but not orthographic reading (DF h2g = .-.16).
• Light et al. (1998). DF h2g for phonological reading = .52; overall reading = .70
• Castles et al (1999): Genetic factors account for twice as much of the variance in
phonological dyslexics as orthographic dyslexic (67% vs. 31%)
• Gayan & Olson (1999): contra Castles et al. (1999) argue that heritable factors play
a significant role in all types of dyslexia.
• Olson et al. (1999) & Wadsworth et al. (2000): genetic factors play a greater role
in reading disability among children with high IQs than low IQs
• Light et al. (1998): RG for overall reading/math = .36 (60% due to genetic factors
common with IQ and 20% due to genetic factors common to phonological reading)
Karin Stromswold (2002). Genetics of Language and Language Disorders
Summary: Twin Language Disorders
• Some language disorders are genetically based (25-100%)
• Genetic factors probably affect the linguistic abilities of disordered
populations more than the general public (75% vs. 25%)
• Genetic language disorders seem to impact different aspects of
language, but less is known about phonology, morphology & syntax
• Unknown if the same genetic factors cause different types of
language disorders (and even if they do, what would this mean?)
• Unclear if the genetic factors identified are specific to language
– The few existing studies have conflicting results, possibly
reflecting aspects of language assessed, methods of assessing etc.
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Vocabulary Studies
• Overall: 8 studies with 1577 MZ, 1389 DZ twins
– Unweighted mean rMZ = .81, rDZ = .57, Falconer’s h2 = .48 (p = .002)
– Weighted mean rMZ = .93, rDZ = .76, Falconer’s h2 = .33 (p < .0001)
• Early: 3 studies with 1247 MZ, 1152 DZ twins 18-24 months old
– Unweighted mean rMZ = .91, rDZ = .78, Falconer’s h2 = .26 (p = .08)
– Weighted mean rMZ = .95, rDZ = .80, Falconer’s h2 = .29 (p < .0001)
• Late: 5 studies with 330 MZ, 237 DZ twins 3-13 years old
– Unweighted mean rMZ = .75, rDZ = .44, Falconer’s h2 = .62 (p = .001)
– Weighted mean rMZ = .71, rDZ = .45, Falconer’s h2 = .53 (p = .02)
• Role of genes increases with age (2 long. studies & meta-analysis)
• Unclear whether genes are specific to language (1 study yes, 1 study
no, 1 longitudinal study yielded different results at different ages)
• Different genes affect normal & impaired twins’ vocabulary:
– Bottom 5%tile TEDS: complete genetic overlap for vocab & nonverbal skills.
– For all TEDS twins, vocabulary-specific genetic factors exist
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Vocabulary Studies
Study
Reznick et al. (1997)
Number of Twin Pairs
144-204 MZ (F > M)
128-172 DZ (M > F)
Ages
14 months
20 months
24 months
Vocabulary Measure
Preferential looking
Expressiv e & receptive
vocabulary (parent report)
Ganger et al. (1999)
57 MZ (27 M, 30 F)
35 DZ (22 M, 13 F)
1008 MZ (466 M, 542
F)
959 DZ (485 M, 474 F)
11 MZ (3 M, 8F)
10 DZ (4 M, 6 F)
x = 18
months
24 months
Age when vocabulary size
= 25 words (diary study )
Vocabulary size at age 2
(MCDI parental report)
3.5 y ears
Stanf ord-Binet
PPVT
Mehrabian Vocabulary
50 MZ (21 M, 29 F)
29 DZ (11 M, 18 F)
53 MZ (25 M, 29 F)
31 DZ (17 M, 16 F)
70 MZ (33 M, 37 F)
35 MZ (22 M, 13 F)
3-6 yrs
x = 4.5
5-12 y rs
x = 7.6
5-13 y rs
x = 8.0
PPVT
Dale et al. (1999)
Fischer (1973)
Mather & Black (1984)
Foch & Plomin (1980)
Segal (1985)
Thompson et al. (1991) 146 MZ, 132 DZ
McCarthy & WISC-R
Vocabulary
WISC-R Vocabulary &
Similarities
Correlation Coefficients
Preferential looking
14 mos rmz = .06; rdz = .07
20 mos rmz = .23; rdz = .24
24 mos rmz = .26; rdz = .21
Expressiv e vocabulary
14 mos rmz = .38; rdz = .37
20 mos rmz = .76; rdz = .63
24 mos rmz = .79; rdz = .60
Receptive vocabulary
14 mos rmz = .64; rdz = .49
20 mos rmz = .68; rdz = .61
24 mos rmz = .71; rdz = .62
rmz = .98; rdz = .92
Falconer’s h2
Preferential looking
14 mos -.02
20 mos -.02
24 mos .10
Expressiv e vocab
14 mos .02
20 mos .26**
24 mos .38***
Receptive vocab
14 mos .30*
20 mos .14
24 mos .18
.12***
rmz = .96; rdz = .82
.28****
Stanf ord rmz = .91; rdz = .45
PPVT rmz = .71; rdz = .48
Mehrabian rmz = .72; rdz = .01
Mean rmz = .78; rdz = .21
rmz = .78; rdz = .44
Stanf ord-Binet .92*
PPVT .46
Mehrabian 1.41*
Mean .94
.68**
rmz = .81; rdz = .68
.26
Vocab rmz = .78 vs. .42
Similar rmz = .76 MZ vs. .29
Mean rmz = .77; rdz = .36
rmz = .60; rdz = .41*
Vocab .72**
Similarities .94***
Mean .82**
.38
6-12 y rs
WISC-R Vocabulary &
x = 9.8
Verbal Fluency
W eighted mean
1247 MZ, 1152 DZ
1.5-2 yrs
rmz = .95; rdz = .80
.29****
W eighted mean
330 MZ, 237 DZ
3-12 y rs
rmz = .71; rdz = .45
.53*
W eighted mean
1577 MZ, 1389 DZ
1.5-12 yrs
rmz = .93; rdz = .76
.33****
Significance lev els are f or one-tailed tests * p < .05; ** p < .01; *** p < .001, **** p < .0001
Number of twins in Reznick et al. (1997) v aried f or dif ferent measures and different ages
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Phonology/Articulation
• Phoneme Discrimation: 21 pairs of 2-3 year olds (Fischer 1973)
– rMZ = .64, rDZ = .53, Falconer’s h2 = .22 (p > .10)
• Phonemic Awareness: 126 pairs of 6-7 year olds (Hohnen & Stevenson 1999)
– Weighted mean rMZ = .90, rDZ = .56, Falconer’s h2 = .68 (p < .001)
– Age 6: 29% IQ-related genetic factors, 23% vocab/morphosyntax, 9% phonology
– Age 7: 18% IQ-related genetic factors, 67% vocab/morphosyntax-related
• Phonological STM: 100 pairs of 7-13 year old twins (Bishop et al. 1999)
– Heritable factors do not affect the ability to repeat sequences of pure tones
– Heritable factors do affect the ability to repeat nonsense words (h2 = .71, p = .01)
• Articulation: 180 pairs of 3-8 yrs (Matheny & Bruggemann ‘73, Mather & Black ‘84)
– Weighted mean rMZ = .93, rDZ = .79, Falconer’s h2 = .26 (p = .03)
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Phonology & Articulation
Study
Bishop et al.
(1999)
Fischer (1973)
Hohnen &
Stevenson
(1999)
Matheny &
Bruggemann
(1973)
Twin Pairs
51 MZ (sex N/A)
49 DZ (sex N/A)
11 MZ (3 M, 8F)
10 DZ (4 M, 6 F)
6 yr 32 MZ, 28 DZ
7 yr 34 MZ, 32 DZ
Age
7-13 y rs
x = 9.9
3.5 y rs
x = 5.8
x = 7.0
Tests
Pure tone repetition
Nonword repetition
Phoneme discrimination
(minimal pairs test)
Phonological awareness
composite score
64 MZ (35 M, 29 F)
37 DZ (16 M, 21 F)
3-8 yrs
Articulation test
3-6 yrs
x = 4.5
Articulation test
Mather & Black 50 MZ (21 M, 29 F)
(1984)
29 DZ (11 M, 18 F)
Correlations
Pure tone rmz = .60; rdz = .49
Nonword rmz = .64; rdz = .29
rmz = .64; rdz = .53
Falconer’s h2
Pure tone .22
Nonword .71**
.22
6 yr olds rmz = .87; rdz = .59
7 yr olds rmz = .92; rdz = .53
Overall r wmz = .90; r wdz = .56
Male rmz = .84; rdz = .56
Female rmz = .90 MZ; rdz = .83
Overall r wmz = ..87; r wdz = .74
SES-M rmz = .85; rdz = .56
SES-F rmz = .90; rdz = .58
Overall-SES r wmz = .90; r wdz = .57
rmz = .96 MZ; rdz = .92 DZ
6 yr olds .56**
7 yr olds .78****
Overall .68***
Male .56*
Female .14
Overall .26
SES-M .58 *
SES-F .64**
Overall-SES .66**
.08
Significance lev els are f or one-tailed tests: * p < .05; ** p < .01; *** p < .001, ****p < .0001
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Morphosyntax
• 12 twin studies of children between 20 months & 12 years.
• Diversity of methods used and aspects of morphosyntax assessed
precludes combining data from these studies, but …
– rMZ significantly greater than rDZ for all measures in 5 studies, 2/3s of measures
in 1 study, and 1/2 of measures in 2 studies. In 4 studies, MZ-DZ differences
were not significant in majority of measures
– rMZ > rDZ in 33 of 36 measures, p < .0001
– Mean rMZ > rDZ for each of 12 studies, p < .0001
– Significant differences were more common in larger studies and in studies that
used ‘cleaner’ measures of morphosyntax
• Do language-specific genes exist?
– Munsinger & Douglass (1976): MZ-DZ difference significant even when
nonverbal IQ partialled out
– Hohnen & Stevenson (1999): Syntax-specific genes account for 20-30%
– Dale et al. (1999): Genetic factors are specific to language but not syntax
(however, parent-report syntax measure is worrisome)
• No evidence that influence of genetics increases with age
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Morphosyntax
Study
Ganger (1998)
Ganger et al.
(1999)
Ganger (1998)
Dale et al. (1999)
Fischer (1973)
Twin Pairs
15 MZ; 9 DZ
16 MZ, 10 DZ
33 MZ (12M, 21 F)
23 DZ (10M, 13 F)
4 MZ, 4 DZ
1008 MZ; 959 DZ
10 MZ (3 M, 8 F)
11 DZ (4 M, 6 F)
Age
Tests and Measures
2.5-3.5 yrs Overregularization & past
tense rates (diary study)
x = 20
Age of f ri st productiv e word
months
combinations (diary study )
2.5-3.5 yrs Tense/Agreement & MLU
(spontaneous speech)
2 yrs
Parent report of syntax
2.5-3.5 yrs Repetition tests
Morphology tests
Grammar comprehension
Analyses of spontaneous
speech
Mittler (1969)
28 MZ (17 M, 11 F)
33 DZ (16 M, 17 F)
4 yr s
Mather & Black
(1984)
50 MZ (21 M, 29 F)
29 DZ (11 M, 18 F)
3-6 yrs
x = 4.5
Koch (1966)
33 MZ
30 DZ
6 yr 32 MZ, 28 DZ
7 yr 34 MZ, 32 DZ
70 MZ (33 M, 37 F)
35 DZ (22 M, 13 F)
37 MZ (14 M, 23 F)
37 DZ (16 M, 21 F)
146 MZ; 132 DZ
6 yrs
Hohnen &
Stevenson (1999)
Segal (1985)
Munsinger &
Douglass (1976)
Thompson et al.
(1991)
x = 5.8
x = 7.0
5-13 y rs
x = 8.0
x mz = 8
x dz = 10
6-12 y rs
x = 9.8
Correlation
Overreg rmz = .97; rdz = .75
Past tense rmz = .97; rdz = .95
rmz = .90; rdz =.50
Tense: r mz . = .83; r dz = 69
MLU: r mz .= .80; r dz = .67
rmz = .85; rdz = .65
MZ-DZ significant for 4 of 10
repetition measures.
MZ-DZ insignificant for both
morphology tests
MZ-DZ significant for grammar
comprehension
MZ-DZ significant for 1 of 4
speech analysis measures
ITPA (Total Score &
Total rmz = .90; rdz = .62
Grammatical Closure,
Grammar rmz = .82; rdz = .59
Verbal Expression, Vocal
Verbal rmz = .63; rdz = .35
Association, and
Assoc rmz = .81; rdz = .63
Comprehension subtests) Compreh rmz = .52; rdz = .72
Berko Morphology
Berko rmz = .97; rdz = .92
ITPA Grammatical Closure Grammar rmz = .68; rdz = .40*
ITPA Verbal Expression
Verbal rmz = .53; rdz = .36
Analysis of grammatical
MZ twins errors more similar in
errors
ty pe & frequency than DZ twins
Composite v ocabulary and 6 yr olds rmz = .80; rdz = .50
morphosyntax
7 yr olds rmz = .90; rdz = .59
General language
rmz = .65; rdz = .43
comprehension test
Composite expressive &
rmz = .83; rdz = .44
receptive morphosyntax
General language
rmz = .87; rdz = .71
achievement test
Falconer’s h2
Overreg .44*
Past tense .04
.81***
Tense .28*
MLU .26
.40***
h 2 = .44
2
Morphology h = -.58
Repetition
Grammar Comp 1.52*
2
Speech analysis h = .82
2
Overall h = .55
Total .56**
Grammar .46*
Verbal .56
Assoc .36
Compreh -.38
Berko .10*
Verbal .34
Grammar .56
No available information
6 yr olds .60*
7 yr olds .62***
.44
.79**
.32***
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Written Language
• Reading: 5 studies with 745 twin pairs
– Weighted mean rMZ = .86, rDZ = .66, Falconer’s h2 = .45, p = .002
– Hohnen & Stevenson (1999): Some genetic factors are specific to language but
not reading (20-30%), with a modest amount specific to reading (20-30%).
Genetic factors common to IQ have only a modest effect (10%), and genetic
factors specific to phonemic awareness have no effect on normal children’s
reading (c.f., dyslexia findings)
• Spelling: 2 studies with 246 twin pairs (Osborne et al, 1968; Stevenson et al, 1987)
– Weighted mean rMZ = .78, rDZ = .48, Falconer’s h2 = .60, p = .002
– Stevenson et al. (1987): Heritabilty estimates are greater for IQ-adjusted scores
than non-adjusted scores (.73 vs. .53)
Karin Stromswold (2002). Genetics of Language and Language Disorders
Normal Twin Reading
Correlation Coefficients
6 yr olds rmz = .95; rdz = .71
7 yr olds rmz = .92; rdz = .61
rmz = .74; rdz = .46
Falconer’s h2
6 yr olds .48***
7 yr olds .62***
.56*
rmz = .94; rdz = .79
.30****
Stevenson et al. (1987) 97 MZ (45 M, 52 F)
107 DZ (48 M, 59 F)
Schonell Reading
96 MZ (45 M, 51 F)
106 DZ (48 M, 58 F)
Osborne et al. (1968)
33 MZ, 12 DZ
13-18 yrs WR Vocabulary Test
Heim Self-judging
Vocabulary Test
Heim Vocabulary Test
Neale Accuracy rmz = .62; rdz = .53
Neale Comp rmz = .71; rdz = .49
Schonell Read rmz = .61; rdz = .51
Mean rmz = .65; rdz = .51
Neale Accuracy .18
Neale Comp .44**
Schonell Read .19
Mean .28
WR Vocab rmz = .61; rdz = .40
Self-judge rmz = .63; rdz = -.13
Heim Vocab rmz = .86; rdz = .38
Mean rmz = .70; rdz = .22
WR Vocab .42
Self-judge 1.53*
Heim Vocab .96**
Mean .96**
W eighted Mean†
rmz = .86; rdz = .66
.41**
Study
Hohnen & Stev enson
(1999)
Foch & Plomin (1980)
Twin Pairs
6 yr 32 MZ, 28 DZ
7 yr 34 MZ, 32 DZ
52 MZ (25 M, 29 F)
32 DZ (17 M, 16 F)
Thompson et al. (1991) 146 MZ; 132 DZ
Age
x = 5.8
x = 7.0
5-12 y rs
x = 7.6
6-12 y rs
x = 9.8
13 yr old
Tests
Composite reading
score
PIAT Word
Recognition Test
Metropolitan Reading
Achievement Test
Neale Reading
Accuracy & Reading
Comprehension Tests
Schonell Reading Test
403 MZ, 342 DZ
Significance lev els are f or one-tailed tests: * p < .05; ** p < .01; *** p < .001, **** p < .0001
† Includes Osborne et al. (1968) and Stev enson et al. (1987) mean data
WR Vocabulary =W ide R ange Vocabulary Test, PIAT = Peabody Individual Achiev ement Test for W ord Recognition
Karin Stromswold (2002). Genetics of Language and Language Disorders
Summary of Twin Results
• Genetic factors play a greater role for languageimpaired people (~1/2 -2/3) than “normals”(~1/4-1/2)
• Genetic factors affect all aspects of language
• Probable existence of some language-specific genes
• Possible existence of some genes specific to different
aspects of language
Karin Stromswold (2002). Genetics of Language and Language Disorders
Potential Worries With Twin Studies
• Gene/environment interactions & the generalizability of
heritability estimates obtained from twins:
– Twins have higher rates of impairments/delays than singletons
– Twins have impoverished prenatal & postnatal environments
• Environmental assumptions:
– Prenatal: Do MZ and DZ twin pairs have the same prenatal environment?
– Postnatal: Do MZ and DZ twin pairs have the same postnatal environment?
– => Swedish Separated-at-Birth Twin Study (Pedersen et al 1994) yielded
similar heritability estimates for reared apart twins as is found for reared
together twins
• Genetic assumptions:
– Are MZ twins genetically identical?
– Are DZ twins genetically equivalent to siblings?
Karin Stromswold (2002). Genetics of Language and Language Disorders
Linkage Studies Background
• Naming conventions
–
–
–
–
Humans have 22 pairs of autosomal & 2 sex (Y, X) chromosomes
Autosomal chromosomes are numbered from 1-22 by size (1 is largest)
Each chromosome has a constriction: short arm (p) long arm (q)
Thus, 15q21 refers to staining band 21 on long arm of chromosome 15
• Multiplex analyses: Compare DNA of affected and unaffected family members
in highly affected SML transmission families. Do marker locus and trait locus assort
independently or is there decreased recombination (indicating 2 loci are neighbors)?
Logarithm of odds score > 3 indicates linkage. LOD of -2 indicates no linkage.
Problem: multiplex analyses reveal genes that can cause SLI, but rarely do
• Sibling pair analyses: Compare DNA of affected and unaffected siblings. If a
trait locus is closely linked to a marker locus, similarity between siblings for the
marker alleles should correspond with phenotypic similarity, regardless of the mode
of transmission (i.e., works with non-SML disorders)
Karin Stromswold (2002). Genetics of Language and Language Disorders
Reported Loci for Dyslexia
1p34-p36 (near Rh region ): Grigorenko et al. 1998, Rabin et al . 1993, Smith, et al. 1991
Also Hussain et al. (2000) reported a case of a balanced reciprocal translation that affects
this region of 1p and segregates with psychomotor delay and dyslexia. Microscopic
deletion of 1p36.1 (Ched rawi et al. 1999, Knigh t-Jones et al. 2000) and monosomy of
1p36.1 (one copy of the 1p36 locus, Slavo tinek et al. 1999) are associated with a
syndrome that includes written and spoken language disorders.
2p15-16:
Fagerheim et al. 1999, Petryshen et al. 2000b
6p21.3-p23 (near HLA region ): Cardon et al. 1994, 1995, Fisher et al. 1999, Gayan &
Olson 1999, Gayan et al. 1995, 1999, Grigorenko et al. 1997, 2000, Petryshen et al. 2000a,
Rabin et al. 1993, Smith et al. 1991)
6q13-16.2: Petryshen et al. 1999b, 2001
11p15.5 (near the dopamine D4 receptor gene): Petryshen et al. 1999c
15q21-q23: Grigorenko et al. 1997, Morris et al. 2000, Nopola-Hemmi et al. 2000, Nöthen
et al. 1999, Pennington and S mith 1988, Schulte-Körne et al. 1998, Smith, et al. 1983
Unclear if different types of dyslexia are linked to different loci
Genetic link (6p21) be tween dy slexia, ADHD, & schizophrenia
Karin Stromswold (2002). Genetics of Language and Language Disorders
The KE Family
KE family: Multiplex family with AD disorder that includes grammatical
deficits (Gopnik 1990), oral dyspraxia (Fisher et al. 1998, Hurst et al. 1990), and
low nonverbal IQ and nonverbal learning disorders (Vargha-Khadem et al. 1995)
Karin Stromswold (2002). Genetics of Language and Language Disorders
7q31 Loci for Spoken Impairments
• Fisher et al. (1998): Disorder in KE family is linked to 7q31
• Tomblin et al. (1998): Linkage of SLI with 7q31 in a populationbased study of second graders
• Lai et al. (2000): The disorder is linked to 7q31.2 in affected KE
family members and an unrelated person with a similar disorder
• Lai et al (2001): All and only affected family KE members have
an abnormal form of the FOXP2 gene. The gene codes for
transcription factor, and is highly expressed in fetal tissue and its
homologue is found in mouse cerebral cortex.
• Enard et al. (2002) : The FOXP2 homologue in non-human
primates (and mouse) differs from that of humans.
• Genetic link between 7q31 and Tourette Syndrome and autism
Karin Stromswold (2002). Genetics of Language and Language Disorders
Other Loci for Spoken Impairments
• Froster et al. (1993): Family with 1p22 and 2q31 translocation
associated with written & spoken impairments
• Elcioglu et al. (1997): Isolated case of severe language delay but
normal nonverbal abilities: Inverted duplication of 15q13->15q2.
• Bartlett et al. (2000): 19 multiplex families with linkage near 4
dyslexia loci (1p36, 2p15, 6p21, 15q21). No linkage to 7q31
• Cholfin et al. (2000): Multiplex family with AD transmission, but
no linkage to 7q31
• SLI consortium (2002): 98 siblings. 16q24 (nonword rep), 19q13
• Bartlett et al. (2002): 5 Canadian multiplex families: 13q21
Karin Stromswold (2002). Genetics of Language and Language Disorders
Going from Loci to Genes
• SLI: Lai et al. (2001): FOXP2 transcription factor gene.
• Dyslexia: possible candidate genes
– 1p34-p36:
– 2p15-p16: phosphotase calcineuron (psychiatric disorders)
– 6p21-p23: HLA (autoimmune), GABA-beta receptor 1 (CNS
inhibitor), lyso-phospholipid coenzyme A acyl transferase (fatty
acid and membrane phospholipid metabolism gene), human
kinesin gene (C elegans mutant have behavioral disorders) ….
– 6q13-16.2:
– 15q21-q23: beta2-microglobin gene (autoimmune); neuronal
tropomodulin 2 & 3 (a major binding protein to brain tropomyosin)
– 11p15.5: dopamine D4 receptor gene
Karin Stromswold (2002). Genetics of Language and Language Disorders
What we don’t know …. Phonology
• Do genetic factors affect phonology (vs. articulation)?
Stromswold & Ganger (in prep): analysis of monthly spontaneous
speech samples (22-47 mo) from 8 sets of normal twins
– Size of phonetic inventory is not more similar for MZ cotwins
– Order of acquisition of phonemes is more similar for MZ cotwins
– Accuracy rate is more similar for MZ cotwins
• Syllable initial: 7.7% vs. 16.4%
• Syllable final: 9.9% vs. 15.9%
– Patterns of errors may be more similar for MZ cotwins
• Substitution rates similar, but MZ cotwins more likely to make the same
substitutions
• MZ cotwins more likely to make the same classes of substitution errors (e.g.,
fronting, voicing errors, stopping)
• Deletion rates more similar for MZ than DZ cotwins
Karin Stromswold (2002). Genetics of Language and Language Disorders
What we don’t know …. Syntax
• To what extent do genetic factors play a role in syntax?
– Published syntax studies generally are small and/or use worrisome
measures
– To do large-scale studies, we need a syntax test that parents can
administer
• The Parent Assessment of Language (PAL)
We’ve designed and are norming a series of parent-administered
test for children ages 3 and above. Each year’s PAL tests
children’s comprehension of syntactic constructions that children
are mastering at that age (actives, passives, reflexive, pronouns,
relative clauses,modals, subjunctives, subject and object control
structures, etc.).
• Longitudinal twin study using the PAL (current N = 120)
Karin Stromswold (2002). Genetics of Language and Language Disorders
PAL Syntax Items (Picture-pointing)
•
Age 3 & Age 4
–
–
•
1 Truncated Active: The bear was licking
3 Truncated Passives: The bear was licked
2 Easy Pronouns: The bear was licking him
1 Full Active: The bear was licking the dog
3 Full Passives: The bear was licked by the dog
1 Easy Reflexives: The bear was licking himself
1 Easy Pronoun: The bear was licking him
1 Truncated Active: The bear was licking
3 Truncated Passives: The bear was licked
1 Med Reflexive: The dog's friend was licking himself
1 Med Pronoun: The dog's friend was licking him
Ages 9 & 10
–
–
–
–
•
1 Full Active: The bear was licking the dog
3 Full Passives: The bear was licked by the dog
2 Easy Reflexives: The bear was licking himself
Ages 7 & 8
–
–
–
–
•
4 Full Passives: The bear was licked by the dog
2 Easy Pronouns: The bear licked him
Age 5 & Age 6:
–
–
–
•
4 Full Actives: The bear licked the dog
2 Easy Reflexives: The bear licked himself
1 Full Active: The bear was licking the dog
3 Full Passives: The bear was licked by the dog
1 Med Refl.: The dog's friend was licking himself
1 Med Pronoun: The dog's friend was licking him
1 Truncated Active: The bear was licking
3 Truncated Passives: The bear was licked
1 Hard Refl: The friend of the dog was licking himself
1 Hard Pronoun: The friend of the dog was licking him
Age 11 and above
All preceded by One of these two dogs is hot and followed by the query Which dog is hot?
–
–
–
–
3 Active Right Branch RC: The bear was licking the dog who __ is hot.
3 Active Center Embed RC: The dog who the bear was licking _ is hot.
3 Passive Right Branch RC: The bear was licked by the dog who __ is hot
3 Passive Center Embed RC: The dog who the bear was licked by __ is hot.
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders
PAL Syntax: Yes/No/Maybe Task (Ages 9+)
• Sally said “Shouldn’t you make the knot tight?”
Did Sally think the knot should be tight?
• Billy won’t go to the park unless John goes.
Will Billy stay home?
• Katie promised Lucy, who was thirsty, to buy juice.
Did Lucy say she would buy juice?
• Mary who is going to the party with Steve does not like to dance.
Does Mary enjoy dancing?
• Michael’s cat chased the mouse and ran away.
Did Michael’s cat run away?
• Jim thinks Tom is bad at sports.
Is Tom bad at sports?
• Maybe the band would have played last night if the drummer hadn’t quit.
Did the band play last night?
• The doctor who was looking for the nurse walked home from the hospital.
Did the doctor walk home from the hospital?
Karin Stromswold (2002). Genetics of Language and Language Disorders
What we don’t know …. Specificity
• Do language-specific genes exist?
– Need more, large studies that assess development in many different areas (not
just cognitive abilities, but also fine motor, gross motor, oral motor, social etc.)
• Do specific genes for different aspects of language exist?
(e.g., syntax-specific, phonology-specific, lexicon-specific)
– Need to assess multiple aspects of language in a large group of children
• Data that we are collecting in our twin study:
– PAL: assesses articulation, lexical access, reading/pre-reading, and syntax
– ASQ: parent assessment of gross motor, fine motor, cognitive, language &
social-emotional skills
– Developmental milestones (gross motor, fine motor, cognitive, language, social)
– Special educational/therapy services
– Neuropsychological diagnoses
Karin Stromswold (2002). Genetics of Language and Language Disorders
Sample PAL (Age 4)
Articulation of onsets:
Rat
Lip
Ship
Cheek
Zip
Jeep
Correct






Incorrect






No response






That
Thin
Spit
Trick
Clock
Frog
Correct






Incorrect






No response






List any sounds the child regularly says wrong, and give a typical mispronounced word
Lexicon: Rapid naming (number of foods named in 30 seconds)
Pre-reading: Capital letter identification.
(Orthographic and phonologic word reading starting at age 6 PAL.)
Syntax: Picture pointing comprehension task
4 actives (e.g., the dog licked the bear)
4 passives (e.g., the fox was tickled by the lion)
2 reflexives (e.g., the cat scratched himself)
2 pronouns (e.g., the monkey splashed him)
Karin Stromswold (2002). Genetics of Language and Language Disorders
What we don’t know …Gene x Environment
• Koeppen-Schomerus et al. (2000): Heritable factors play a negligible role in
linguistic and cognitive abilities of very premature TEDS twins.
• What is the relative importance of prenatal and postnatal environment?
– We are comparing heritability estimates for twins with easy/hard prenatal courses
•
•
•
•
•
•
Gestational age
Birthweight
Birthweight percentile
Brain injuries
Short (discharged before or by due date ) vs. long hospital stays
Composite neonatal morbidity measure
– We are comparing heritability estimates for twins with different postnatal environments
(SES, therapeutic interventions, traditional vs. developmental NICUs)
• Are there specific perinatal factors that place twins at risk (e.g., steroids,
MgSO4, intrauterine infection, placental infarction, ventilation, TTTS, etc.)?
• Quantifying the role of prenatal environment: we are comparing outcomes for
MZ twins with very similar birth weights and very different birth weights (MZS MZD ) and DZ twins with similar/different birth weights
Karin Stromswold (2002). Genetics of Language and Language Disorders
What we don’t know … Going from genes to disorders
• The genotype to phenotype mapping problem
– One Genotype:Many Phenotypes / One Phenotype:Many Genotypes
• The developmental problem: phenotypes change
• Direct vs. indirect genetic effects: The case of clotting disorders
– Indirect: If a mother has a genetic clotting disorder, her children are at risk even
if they not carry the mutation.
– Direct: A child with a genetic clotting disorder is at risk for perinatal strokes
(and the “language” areas of the brain are particularly vulnerable)
– Maternal/child interactions possible when both have the disorder
– Environmental interactions: high estrogen, low folic acid, delayed child-bearing
• Specificity problem:
– Familial Dysautonomia (9q31; IKBKAP). AR disorder with normal IQs and
profound oral motor dyspraxia (but they also have ANS problems)
– FOXP2: Do people with 7q31-linked autism and Tourette Syndrome have the
FOXP2 mutation?
• “Just so” stories
Karin Stromswold (2002). Genetics of Language and Language Disorders
What if Language is Like Height?
• Quantative Trait Loci (QTLs): Multifactorial-polygenic
Hypothesis: In normal people (and in most language-impaired
people), variance in linguistic ability results from many genes
(each of which has a small effect) acting together and in
combination with the environment. Thus, linguistic abilities are
normally distributed, and the observed heritability is due to QTLs
• How to find language QTLs
– People practice linguistic assortative mating.
– Assortative mating increases genetic variance in successive generations
– Assortative mating & additive genetic variances makes QTLs easier to find
– It is easier to detect QTLs by looking at the high end of the distribution (at the
low end, random mutations & environmental insults obscure QTL effects)
– Linguists (particularly second generation linguists) should donate their DNA
Karin Stromswold (2002). Genetics of Language and Language Disorders
Karin Stromswold (2002). Genetics of Language and Language Disorders

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