TABLE 2.

Summary of imaging genetics findings related to reading/language

Gene	Reference(s)	Variant(s)	Design	Imaging	Na	Agea,b	Ethnic Backgrounda	Imaging findings	Behavioral findings
BDNF	Jasinska et al. (2016)	rs6265**	Continuous	fMRI	81	6–10	70 Caucasian 1 African-American 2 Hispanic 3 Asian 5 Mixed ethnicity	Increased activation bilaterally in Met carriers relative to Val/Val homozygotes	Val allele homozygotes performed better than Met carriers on passage comprehension, phonological memory, and IQ
C2ORF3/MRPL19/GCFC2	Eicher et al. (2016)	rs2298948* rs917235*⊥ rs6732511*⊥ ⊥DYX3 locus upstream of GCFC2 and MRPL19	Continuous	MRI DTI	332	3-20	European	Minor allele on rs2298948 associated with decreased CT and GMV. rs917235 associated with CT rs6732511 minor allele associated with increased GMV	NR
	Scerri et al. (2012)	rs917235***** rs714939 rs1000585	Continuous	MRI DTI	76	6–25	98% European	G allele associated with reduced WMV	rs714939 and rs917235 associated with verbal IQ
CMIP	Skeide et al. (2016)	rs12927866 rs6564903 rs3935802 rs4265801 rs16955705 rs7201632 Joint SNP effect*****	Case/control	MRI	54	5–12	NR	CMIP related to bilateral portions of cerebellar WM	Associated with reading comprehension
COL4A2	Skeide et al. (2016)	rs9521789*****	Case/control	MRI	54	5–12	NR	Related to cerebellar GMV	No significant associations reported
COMT	Landi et al. (2013)	rs4680****	Case/control	fMRI	86	6–10	83 Caucasian 3 African-American	Greater activation in left hemisphere reading-related regions for Met carriers	Significant differences between genotype groups in phonological awareness (PA) and spelling
NRSN1	Skeide et al. (2016)	rs9356928 rs4285310 rs3178 Joint SNP effect*****	Case/control	MRI	54	5–12	NR	Joint SNP association with GMV and WMV	NRSN1 associated with reading comprehension performance. GMV in VWFA ROI related to NRSN1 predicted reading outcomes
ROBO1	Lamminmäki et al. (2012)	N/A	Case/control	MEG	10	19–51	Finnish	Ipsilateral auditory suppression in both hemispheres related to ROBO1 expression levels	NR
CCDC136/FLNC	Gialluisi, Guadalupe, Francks, and Fisher 2017	rs59197085 rs56184882** rs339054** rs339046**	Continuous	MRI	1275	18–35	NR	Associated with cortical surface area in IFG	NR
DCDC2	Cope et al. (2012)	rs793862 rs807701 rs807724 BV677278 STR** BV677278 del. rs1087266	Continuous	fMRI	82	7–12	European American	DCDC2 variants associated with activation during print and auditory processing Nominal associations between DCDC2 variants and activation during word reading and nonword reading tasks	Nominally significant associations between DCDC2 variants and measures of IQ, PA, word reading, and passage comprehension
	Czamara et al. (2011)	Chr6:24459391/rs1052724905** Chr6:24564881** Chr6:24571041** Chr6:24581378/rs1033367480**	SRD	EEG	200	8–19	German	Four rare variants on DCDC2 or between DCDC2 and KIAA0319 were associated with late mismatch negativity (MMN) to speech	NR
	Darki et al. (2012)	rs793842***** rs793862 rs807701 rs2328819 rs2792682 rs7751169 rs9460974	Continuous	MRI DTI	76	6–25	98% European	Associated with WMV	Positive correlation between white matter volume and reading scores. No direct relationships between SNPs and behavior.
	Darki et al. (2014)	rs793842*****	Continuous	MRI DTI	76	6–25	98% European	Associated with WMV in left temporo-parietal region and with CT in left temporo-parietal and occipital cortices	Associated with reading comprehension scores; WMV and CT correlated with reading scores
DCDC2	Eicher et al. (2016)	rs707864	Continuous	MRI DTI	332	3–20	European	NS	NR
	Marino et al. (2014)	DCDC2-intron2 deletion**	Case/control	DTI	47	16–21	NR	Reduced WM integrity in subjects with DCDC2 intron2 deletion	Positive correlation between fractional anisotropy (FA) and average reading scores
	Meda et al. (2008)	DCDC2-intron2 deletion*	Continuous	MRI	56	19–85	NR	Increased GMV in carriers of DCDC2 intron 2 deletion compared to those homozygous for no deletion	NR
DYX1C1	Darki et al. (2012)	rs3743204**** rs3743205 rs17819126	Continuous	MRI DTI	76	6–25	98% European	Associated with WMV in bilateral temporo-parietal region	Significant correlation between WMV and reading scores
	Darki et al. (2014)	rs3743204*****	Continuous	MRI DTI	76	6–25	98% European	Associated with bilateral temporo-parietal WMV, replicating findings of Darki et al. (2012) across an additional time point	Significant correlation between WMV and reading scores
FOXP2	Belton et al. (2003)	KE Family***	Case/control	MRI	34	9–27	European	Altered GM density in affected family members	NR
	Liegois et al. (2003)	KE Family***	Case/control	fMRI	20	19–56	European	Affected family members showed an atypical pattern of activation in a verb generation task compared to unaffected family members and controls	NR
FOXP2	Pinel et al. (2012)	rs10249234*** rs7784315*** rs7812028* rs17137135*** rs6980093*** rs6942634 rs2894699 rs1476535 rs10255943 rs10486026 rs10261780 rs10262103 rs4727799 rs17312686 rs2106900 rs17312861 rs12113612 rs10266297 rs10279936 rs7799109 rs12532920 rs17137124 rs10269986 rs1229761 rs1229758 rs12705966 rs10230087 rs7782412 rs1456029 rs12670585 rs6966051 rs17213159 rs1378771 rs12705971 rs12705973 rs2396766 rs12671330	Continuous	fMRI	94	M = 24.7	European	Associations with activation during a sentence reading task	NR
FOXP2	Skeide et al. (2016)	rs923875 rs12533005 rs6980093 rs10230558 rs7782412 rs936146 Joint SNP effect*****	Continuous	MRI	54	5–12	NR	Joint SNP effect related to GMV in left medial superior frontal gyrus	NS
	Vargha-Kadem et al. 1998	KE Family***	Case/control	PET MRI	34	NR	European	Atypical activation during a word repetition task in affected family members. Regional alterations in GM structure	Affected family members show deficits in word repetition, nonword repetition, and simultaneous and sequential orofacial movements
	Watkins et al. (2002)	KE Family***	Case/control	MRI	34	9–27	European	Atypical pattern of GMV in affected family members compared to unaffected family members and controls	Correlation between caudate nucleus volume and performance on test of oral praxis, nonword repetition, and coding subtest of Wechsler Intelligence Scale in affected family members
	Wilcke et al. (2012)	rs12533005**	Case/control	fMRI	33	M = 11	German	Decreased activation in risk allele carriers during rhyme decision task	NR
	Darki et al. (2012)	rs6935076***** rs4504469 rs2143340	Continuous	MRI DTI	76	6–25	98% European	Associated with left temporoparietal WMV	Positive correlations between WMV and reading comprehension and WMV and timed single-word reading; No significant correlations between SNPs and reading
KIAA0319	Darki et al. (2014)	rs6935076*****	Continuous	MRI DTI	76	6–25	98% European	Associated with bilateral temporoparietal WMV, replicating findings from Darki et al. (2012) across an additional time point	Significant correlation between WMV and reading scores
	Eicher et al. (2016)	rs9461045**** rs9295626 rs10456309 rs4576240	Continuous	MRI DTI	332	3–20	European	Associated with cortical thickness and WM integrity	NR
	Pinel et al., 2012	rs2235676 rs9467247 rs3756821	Continuous	fMRI	94	M = 24.7	Primarily Caucasian	NS	NR
RBFOX2	Gialluisi et al. (2017)	rs5995177*** rs78563107*** rs6000084*** rs6000085*** rs144006011***	Continuous	MRI	1275	18–35	NR	Associated with cortical thickness	NR
SETBP1	Perdue et al. (2019)	rs7230525***	Continuous	fMRI	73	5–12	116 Caucasian 2 African American 3 Hispanic 4 Asian 8 mixed 2 unreported	Interaction between genotype, lexicality and modality in the right inferior parietal lobule	Genotype associated with phonological working memory
SLC2A3	Roeske et al. (2011)	rs4234898*** rs11100040***	SRD	EEG	200 18 6c***	8–19	German	Altered late MMN response	NR
	Skeide et al. (2015)	rs4234898 rs11100040***	Continuous	rsfMRI DTI	34	9–12	NR	Weaker functional and structural connectivity in risk allele carriers	WM integrity related to PA performance
THEM2/ACOT13	Eicher et al. (2016)	rs3777663**	Continuous	MRI DTI	332	3–20	European	Associated with cortical thickness	NR
	Pinel et al. (2012)	rs17243157*** rs3756819 rs1061925 rs3181227 rs2223588 rs6928074 rs9461049 rs926529 rs1885211	Continuous	fMRI	94	M = 24.7	Primarily Caucasian	Associated with functional asymmetry during reading and speech listening tasks	NR
CNTNAP2	Dennis et al. (2011)	rs2710102***	Continuous	DTI	328	M = 23.4	Caucasian	Atypical structural connectivity indices in risk allele carriers	NR
	Koeda et al. (2015)	rs7794745*** rs2710102	Continuous	fMRI	108	M = 26.3	Japanese	Genotype group differences in activation during general auditory processing, human voice processing, and language processing	NS
	Skeide et al. (2016)	rs7794745 rs10246256 rs2710102 rs759178 rs17236239 rs4431523 rs2710117 Joint SNP effect*****	Continuous	MRI	54	5–12	NR	Joint SNP effect related to WMV in left cerebral and cerebellar peduncles	Association with reading comprehension
CNTNAP2	Tan et al. (2010)	rs7794745***	Continuous	MRI DTI	114	NR	NR	Reduced GMV, WMV, and WM integrity in risk allele homozygotes	NR
	Udden et al. (2017)	rs7794745****	Continuous	MRI	1717	M = 24.3	Primarily European Caucasian	Reduced GMV in AT/TT carriers compared to AA homozygotes	NR
	Whalley et al. (2011)	rs7794745*** rs2710102***	Continuous	fMRI	66	M = 20.5	Caucasian	Atypical patterns of activation in risk allele carriers during sentence completion task	NS

Note. Shading indicates relevant phenotype: white = reading, light gray = reading and/or language, dark gray = language. Boldface indicates SNPs for which significant imaging-genetic results were reported. For studies that included corrected and uncorrected p values, asterisks indicate corrected p to be consistent with other studies presented here.

Abbreviations: CT, cortical thickness; GMV, gray matter volume; NR, not reported; NS, no significant findings; WMV, white matter volume.

^*p < .01, uncorrected.

^**p < .001, uncorrected.

^***p < .05, corrected.

^****p < .01, corrected.

^*****p < .001, corrected.

^aInformation listed refers to samples included in neuroimaging analyses.

^bAge ranges or means reported according to information available in each study.

^cReplication sample.