GRIN2B predicts attention problems among disadvantaged children
Valentina Riva, Marco Battaglia,Maria Nobile, Francesca Cattaneo, Claudio Lazazzera, Sara Mascheretti, Roberto Giorda,Chantal Mérette, Claudia Émond, Michel Maziade, Cecilia Marino
Cecilia Marino, MD, Ph D
Centre de Recherche de l’Institut Universitaire en Santé Mentale de Québec
Department of Psychiatry and Neuroscience, Laval University
2601, chemin de la Canardière
Québec
(Québec), Canada G1J 2G3
Phone: 418-663-4534
e-mail address:
Table S1. Allele and genotype frequencies and Hardy-Weinberg Equilibrium for GRIN2B markers (n= 625).
GRIN2B markers / allele frequency / genotype frequency / Hardy-WeinbergEquilibrium
p-valuesa
rs5796555 / - / 0.75 / -/- / -/A / A/A / .9999
A / 0.25 / 57.0 / 36.9 / 6.0
rs1012586 / G / 0.70 / G/G / G/C / C/C / .7295
C / 0.30 / 47.9 / 43.4 / 8.7
rs2268119 / A / 0.76 / A/A / A/T / T/T / .5842
T / 0.24 / 57.5 / 36.8 / 5.7
rs2216128 / A / 0.77 / A/A / A/G / G/G / .6526
G / 0.23 / 60.6 / 33.8 / 5.6
rs11609779 / C / 0.82 / C/C / C/T / T/T / .3777
T / 0.18 / 66.9 / 29.2 / 3.9
rs2192973 / G / 0.76 / G/G / G/A / A/A / .0016
A / 0.24 / 60.1 / 31.7 / 8.3
a Bonferroni corrected p-value threshold for significance= .0083
Table S2.Descriptive statistics of log-transformed behavioral measures (n= 625)
Social problems / 1.70 / 1.97 / 1.73 (.04) / 1.40 / 2.80
Thought problems / 1.70 / 1.90 / 1.73 (.04) / 1.50 / 1.51
Attention problems / 1.70 / 1.94 / 1.74 (.04) / 1.36 / 1.47
Rule-breaking behavior / 1.70 / 1.86 / 1.72 (.03) / 1.84 / 3.62
Aggressive behavior / 1.70 / 1.91 / 1.73 (.04) / 1.54 / 1.96
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Table S3. Pearson’s r bivariate correlations among cognitive and behavioral measures (n= 625)
IQ vocabulary / IQ block design / IQ memory / Rey complex figure / Anxious/depressed / Withdrawn/depressed / Somatic complaints / Thought problems / Attention problems / Aggressive behaviorIQ vocabulary / - / .22 / .22 / .14 / -.02 / -.09 / -.06 / -.02 / -.16 / -.09
IQ block design / <.001 / - / .20 / .28 / -.01 / -.02 / .04 / .07 / -.04 / -.02
IQ memory / <.0001 / <.0001 / - / .15 / -.05 / -.01 / -.08 / -.01 / -.12 / -.07
Rey complex figure / .0006 / <.0001 / <.0001 / - / -.02 / .02 / -.03 / -.01 / -.09 / -.06
Anxious/depressed / .5981 / .7477 / .2434 / .6044 / - / .53 / .41 / .54 / .49 / .50
Withdrawn/depressed / .0340 / .7303 / .7432 / .6063 / <.0001 / - / .32 / .35 / .40 / .40
Somatic complaints / .1930 / .3226 / .0456 / .5633 / <.0001 / <.0001 / - / .47 / .34 / .35
Thought problems / .6683 / .0804 / .8149 / .8025 / <.0001 / <.0001 / <.0001 / - / .47 / .53
Attention problems / <.0001 / .3225 / .0030 / .0244 / <.0001 / <.0001 / <.0001 / <.0001 / - / .60
Aggressive behavior / .0307 / .6615 / .1117 / .1431 / <.0001 / <.0001 / <.0001 / <.0001 / <.0001 / -
Lower diagonal: two-sided p-values; upper diagonal: Pearson’s r; Bonferroni corrected p-value threshold for significance= .0011
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Table S4. Pearson Chi-Squares (p-values) applied to contingency tables testing associations between each pair of GRIN2B marker and environmental measure (n= 625)
GRIN2B markersEnvironmental measures / rs5796555 / rs1012586 / rs2268119 / rs2216128 / rs11609779
Socioeconomic status / 1.76 (.4141) / .80 (.6694) / 1.46 (.4831) / 1.22 (.5446) / 3.03 (.2196)
Maternal smoke during pregnancy / 4.36 (.1132) / 1.56 (.4579) / 1.61 (.4466) / .32 (.8531) / .89 (.6421)
Gestational age at birth / 7.96 (.0187) / 3.57 (.1679) / 2.25 (.3247) / 8.27 (.0160) / 3.94 (.1395)
Breastfeeding / 1.63 (.4429) / 1.58 (.4537) / .05 (.9750) / 1.67 (.4334) / .56 (.7573)
Bonferroni corrected threshold for significance was set at p= .0025
Table S5 Interaction effects between GRIN2B markers and environmental factors from 80 two-way ANOVAs upon cognitive phenotypes (n=625)
Marker / F statistic / p-value / Effect sizea
Socio-economic status
rs5796555 / .33 / .7160 / .001
rs1012586 / .24 / .7863 / .001
rs2268119 / .60 / .5520 / .002
rs2216128 / 1.80 / .1670 / .006
rs11609779 / 2.05 / .1300 / .007
Maternal smoking during pregnancy
rs5796555 / .04 / .9630 / .0001
rs1012586 / 1.07 / .3449 / .004
rs2268119 / 1.12 / .1209 / .007
rs2216128 / 2.01 / .1345 / .007
rs11609779 / 1.24 / .2916 / .004
Gestational age
rs5796555 / .58 / .5597 / .002
rs1012586 / 1.83 / .1618 / .007
rs2268119 / .93 / .3954 / .003
rs2216128 / 1.00 / .3688 / .004
rs11609779 / .48 / .6164 / .002
Breastfeeding
rs5796555 / .24 / .7836 / .001
rs1012586 / 2.76 / .0639 / .009
rs2268119 / .69 / .5037 / .002
rs2216128 / .25 / .7810 / .001
rs11609779 / 1.24 / .2913 / .004
IQ block design
Marker / F statistic / p-value / Effect sizea
Socio-economic status
rs5796555 / .24 / .7863 / .001
rs1012586 / .58 / .5592 / .002
rs2268119 / .98 / .3755 / .003
rs2216128 / .92 / .3981 / .003
rs11609779 / .85 / .4294 / .003
Maternal smoking during pregnancy
rs5796555 / .24 / .7889 / .001
rs1012586 / .03 / .9708 / .0001
rs2268119 / .37 / .7010 / .001
rs2216128 / .48 / .6170 / .002
rs11609779 / 1.43 / .2410 / .005
Gestational age
rs5796555 / 2.09 / .1244 / .008
rs1012586 / 3.60 / .0281 / .013
rs2268119 / 1.58 / .2070 / .006
rs2216128 / .54 / .5861 / .002
rs11609779 / .30 / .7377 / .001
Breastfeeding
rs5796555 / 4.41 / .0126 / .015
rs1012586 / 2.93 / .0543 / .010
rs2268119 / .11 / .8958 / .0004
rs2216128 / .45 / .6391 / .002
rs11609779 / 1.20 / .3010 / .004
IQ memory
Marker / F statistic / p-value / Effect sizea
Socio-economic status
rs5796555 / .06 / .9385 / .00002
rs1012586 / .88 / .4137 / .003
rs2268119 / 1.90 / .1511 / .006
rs2216128 / 1.53 / .2170 / .005
rs11609779 / .64 / .5282 / .002
Maternal smoking during pregnancy
rs5796555 / .49 / .6136 / .002
rs1012586 / .43 / .6486 / .001
rs2268119 / .06 / .9340 / .00002
rs2216128 / .80 / .4492 / .003
rs11609779 / .10 / .9033 / .0003
Gestational age
rs5796555 / 6.62 / .0014 / .023
rs1012586 / 4.77 / .0088 / .017
rs2268119 / 3.15 / .0438 / .011
rs2216128 / 5.87 / .0030 / .020
rs11609779 / .03 / .9684 / .0001
Breastfeeding
rs5796555 / 3.18 / .0423 / .011
rs1012586 / 5.48 / .0044 / .018
rs2268119 / .04 / .9565 / .0001
rs2216128 / 3.95 / .0198 / .013
rs11609779 / .53 / .5913 / .002
Rey complex figure
Marker / F statistic / p-value / Effect sizea
Socio-economic status
rs5796555 / .59 / .5559 / .002
rs1012586 / 3.64 / .0268 / .013
rs2268119 / .86 / .4225 / .003
rs2216128 / .19 / .8259 / .001
rs11609779 / .65 / .5239 / .002
Maternal smoking during pregnancy
rs5796555 / .31 / .7323 / .001
rs1012586 / .37 / .6940 / .001
rs2268119 / .11 / .8999 / .0004
rs2216128 / .68 / .5057 / .002
rs11609779 / 1.09 / .3371 / .004
Gestational age
rs5796555 / 3.78 / .0234 / .014
rs1012586 / 2.40 / .0918 / .009
rs2268119 / .37 / .6929 / .001
rs2216128 / .12 / .8872 / .0004
rs11609779 / .29 / .7454 / .001
Breastfeeding
rs5796555 / .38 / .6875 / .001
rs1012586 / .12 / .8912 / .0004
rs2268119 / .72 / .4878 / .003
rs2216128 / .38 / .6813 / .001
rs11609779 / .88 / .8748 / .0004
a Partial eta-squared. The Bonferroni-corrected threshold to infer significance was set to .0005
Table S6Odds ratios for attention according to presence of genetic (G) and/or envirmental (E) risk factors
Attention / Risk Ec / Non-risk Ed / Risk Ge / Non-risk Gf / Risk G+Eg / Non-risk G+EhTotal sample n= 603 / 98 / 505 / 252 / 351 / 43 / 560
Impaireda n= 49 / 13 / 36 / 27 / 22 / 11 / 38
Not-impairedb n= 554 / 85 / 469 / 225 / 329 / 32 / 522
Odds ratio (95% CI) / 1.99 (1.01-3.91) / 1.79 (.10-3.23) / 4.72 (2.21-10.10)
aCBCL/6-18 attention problems 65, i.e. +1.5 standard deviation
bCBCL/6-18 attention problems < 65, i.e. < +1.5 standard deviation
csocioeconomic status 30
dsocioeconomic status > 30
ers2268119 A/A and A/T
frs2268119 T/T
g socioeconomic status 30 + rs2268119 A/A or A/T
h socioeconomic status 30 + rs2268119 T/T; socioeconomic status > 30 + rs2268119 A/A or A/T or T/T
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