Supplementary Material

Population characteristics

Site ASD Controls (N = 636 [86 ♀, 550 ♂]) (n = 839 [202 ♀, 637 ♂]) ​ ​ ​ ​ ​ ​ ​ ​

BNI 1 (n = 58, [58♂]) N= 29 [29♂] N = 29 [29♂] ​ ​ ​ ​ ​ ​ ETH 1 (n = 31, [31♂]) N = 9, [9♂] N = 22, [22♂] ​ ​ ​ ​ ​ ​ GU 1 (n = 78, [50♂, 28♀]) N = 32 [27♂, 5♀] N = 46 [23♂, 23♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ IP 1 (n = 6, [4♂, 2♀]) N =4 [3♂, 1♀] N = 2 [1♂, 1♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ IU 1 (n = 7 [5♂, 2♀]) N = 1[1♀] N = 6 [5♂, 1♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ KKI 1 (n = 122 [79♂, 43♀]) N= 32 [24♂, 8♀] N = 90 [55♂, 35♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ KKI 2 (n = 49 [35♂, 14♀]) N = 12 [8♂, 4♀] N = 37 [27♂, 10♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ KKI 3 (n = 57 [39♂, 18♀]) N = 15 [12♂, 3♀] N = 42 [27♂, 15♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ NYU (n = 227 [186♂, 41♀]) N= 101 [86♂, 15♀] N = 126 [100♂, 26♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ OHSU (n = 117 [82♂, 35♀]) N = 47 [41♂, 6♀] N = 70 [41♂, 29♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ OLIN 1 (n = 20 [17♂, 3♀]) N = 9 [8♂, 1♀] N= 11 [9♂, 2♀] nd​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ONRC_2 :OLIN 2 sample​ (n = 48 [32♂, N = 17 [14♂, 3♀] N = 31 [18♂, 13♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 16♀]) ​ ​ SDSU (n = 67 [55♂, 12♀]) N = 32 [25♂, 7♀] N = 35 [30♂, 5♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ TRINITY (n = 47 [47♂]) N = 24 [24♂] N = 23 [23♂] ​ ​ ​ ​ ​ ​ TCD_1 (TRINITY 2nd sample) (n = 36 N = 16 [16♂] N = 20 [♂, ♀] ​ ​ ​ ​ ​ ​ ​ [36♂]) ​ ​ UCD 1 (n = 27 [20♂, 7♀]) N = 15 [12♂, 3♀] N = 12 [8♂, 4♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ UCLA Abide1 (n = 83 [71♂, 12♀]) N = 46 [40♂, 6♀] N = 37 [31♂, 6♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ UCLA Abide2 (n = 19 [15♂, 4♀]) N = 9 [9♂] N = 10 [6♂, 4♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ USM (n = 125 [120♂, 5♀]) N = 67 [65♂, 2♀] N = 58 [55♂, 3♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ CALTECH (n = 34 [27♂, 7♀]) N = 15 [12♂, 3♀] N = 19 [15♂, 4♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ CMU (n = 22 [16♂, 6♀]) N = 11 [8♂, 3♀] N = 11 [8♂, 3♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ LEUVEN (n = 58 [51♂, 7♀]) N = 28 [26♂, 2♀] N = 30 [25♂, 5♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ MAX MUN (n = 35 [28♂, 7♀]) N = 14 [11♂, 3♀] N = 21 [17♂, 4♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ PITT (n = 54 [46♂, 8♀]) N = 27 [23♂, 4♀] N = 27 [23♂, 4♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ UM (n = 24 [20♂, 4♀]) N = 11 [8♂, 3♀] N = 13 [12♂, 1♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ YALE (n = 24 [17♂, 7♀]) N = 13 [10♂, 3♀] N = 11 [7♂, 4♀] ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​

Supplementary Table 1: Distribution of Patients and Controls by Centres. 8 centres participated to Abide 1 and Abide 2 data: in bold in ​ the table. Abbreviations corresponding to the centres: BNI_1 (Barrow Neurological Institute), ETH_1 (ETH Zurich), GU (Georgetown University), IP_1 (Institut Pasteur and Robert Debre Hospital), IU_1 (Indiana University), KKI_1 (Kennedy Krieger Institute), NYU (NYU) Langone Medical Center), OHSU (Oregon Health and Science University), OLIN_1 and OLIN_2 (ONRC: Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, samples 1 and 2), SDSU (San Diego State University), TRINITY (Trinity Center for Health Sciences), UCD_1 (University of California Davis), UCLA_1 (University of California Los Angeles, sample 1), UCLA_2 (University of California Los Angeles, sample 2), USM (University of Utah, School of Medicine), CALTECH ( California Institute of Technology), CMU (Carnegie Mellon University), LEUVEN_1 (University of Leuven, sample 1), LEUVEN_2 (University of Leuven, sample 2), MAX_MUN (Ludwig Maximilians University Munich), PITT (University of Pittsburgh School of Medicine) , UM (University of Michigan), Yale (Yale Child Study Center)

Comorbidities ASD Controls ADHD (n = 96) N = 94 N = 2 Phobia (n = 40) N = 28 N = 12 ODD (n = 12) N = 11 N = 1 Anxiety Disorder (n = 34) N = 31 N = 3 Mood Disorder (n = 12) N = 12 Enuresis / Encopresis (n = 12) N = 10 N = 2 Troubles des conduites (n = 2) N = 2 Obsessions (n = 21) N = 13 N = 8 Compulsions (n = 1) N= 1 PTSD (n = 8) N = 7 N = 1 Somatization Disorder (n = 1) N = 1 Schizoid Personality (n = 1) N = 1 Manic episode (n = 1) N = 1

Supplementary Table 2: Summary of comorbidities identified in the studied population. ADHD = Attention Deficit with Hyperactivity ​ Disorder. The phobia item includes patients suffering from social phobia and specific phobia. ODD: Oppositional Defiant Disorder. The "anxiety disorder" item includes patients with anxiety, separation anxiety, and generalized anxiety disorder. The 3 identified controls had a generalised anxiety disorder. Regarding the Enuresis / Encopresis item: 9 individuals had enuresis (7 ASD patients and 2 controls), and 3 ASD patients had encopresis. PTSD = Post Traumatic Stress Disorder. No comorbidities of schizophrenia, antisocial personality disorder, anorexia nervosa, bulimia, or substance abuse were found in either controls or ASD subjects.

Cortical regions with GWPC differences between individuals with ASD and controls

Depth of GMI Cortical regions Hsph Number of Number of Cluster Mean chosen for vertex resolution corrected difference GWPC points éléments p-value (%) calculation

0% precuneus, cuneus, isthmus of the R 865 2.589 6.81e-03 0.261 cingulate cortex, pericalcarine region

10% Pericalcarine region, precuneus, L 2521 6.131 0.352 cuneus, lingual cortex 4.91e-08

Paracentral fissure, precuneus, L 2209 3.688 0.364 posterior cingulate cortex 1.5e-4

Upper and transverse temporal gyrus, L 1451 3 0.385 insula, supramarginal gyrus 1.44e-03

Lateral occipital cortex, cuneus, L 1072 2.538 6.58e-03 0.381 pericalcarine region precuneus, cuneus, pericalcarine R 1176 2.787 2.9e-03 0.37 region, isthmus of the cingulate gyrus, lingual cortex 20% Lateral occipital cortex, pericalcarine L <1e-100 0.455 region, lingual cortex, precuneus, 5395 12.078 cuneus, lower parietal cortex

Upper and transverse temporal gyrus, L 3238 0.502 upper temporal sulcus, supramarginal 6.278 2.76e-8 gyrus, insula, middle temporal gyrus

Paracentral sulcus, precentral and L 2398 3.679 1.41e-04 0.479 postcentral gyrus, precuneus, posterior cingulate cortex Lateral occipital cortex, cuneus, R 1655 3.601 1.82e-04 0.446 pericalcarine precuneus, cuneus, pericalcarine R 1276 2.799 2.54e-03 0.476 region, lingual gyrus, isthmus of the cingulate gyrus 30% Lateral occipital cortex, pericalcarine L <1e-100 0.537 region, lingual cortex, precuneus, 7093 15.072 cuneus, lower parietal cortex

Upper temporal gyrus, lower parietal L 3958 7.79e-10 0.565 gyrus, transverse temporal gyrus, 7.356 upper temporal sulcus, supramarginal

gyrus, insula Paracentral fissure, pre- and L 2643 5.52e-05 0.561 postcentral gyri, precuneus, posterior 3.957 cingulate cortex

Occipital lateral gyrus, cuneus, R 1999 0.525 pericalcarine region, lingual cortex, 4.089 3.56e-05 superior parietal gyrus

precuneus, cuneus, pericalcarine R 1562 3.368 0.531 region, lingual cortex, isthmus of the 3.8e-04 cingulate cortex

40% Lateral occipital cortex, pericalcarine L 8397 17.122 0.574 region, lingual cortex, precuneus, <1e-100 cuneus, inferior and superior parietal

gyrus Upper, middle and transverse L 3898 7.361 7.74e-10 0.588 temporal gyrus, upper temporal sulcus, lower parietal gyrus, supramarginal cortex, insula Paracentral, pre- and postcentral gyri, L 2913 4.369 1.44e-05 0.605 precuneus, posterior cingulate cortex Lateral occipital cortex, cuneus, R 0.576 2138 4.249 2.12e-05 pericalcarine region, lingual cortex, superior parietal cortex precuneus, pericalcarine region, R 0.537 1885 4.017 4.54e-05 lingual cortex, cuneus, isthmus of the cingulate cortex 50% Lateral occipital cortex, pericalcarine L 8463 17.067 <1e-100 0.591 region, precuneus, cuneus, lingual cortex, upper and lower parietal cortex

Paracentral, pre- and postcentral gyri, L 3111 4.862 2.91e-06 0.614 precuneus, posterior cingulate cortex Upper and transverse temporal gyri, L 1318 2.58 0.00526 0.607 insula, supramarginal gyrus Lower parietal gyrus, middle temporal L 1098 2.113 0.0243 0.58 gyrus, superior temporal sulcus Pre- et postcentral gyri L 1094 1.925 0.045 0.721 Lateral occipital cortex, cuneus, R 0.603 2094 4.038 4.33e-05 pericalcarine region, lingual cortex, superior parietal cortex precuneus, cuneus, pericalcarine R 0.579 1226 2.517 0.00639 region, isthmus of the cingulate cortex 60% Lateral occipital cortex, pericalcarine L 7346 14.01 <1e-100 0.598 region, inferior and superior parietal cortex, precuneus, cuneus, lingual cortex, Paracentral fissure, precuneus, L 1798 2.837 0.00229 0.562 posterior cingulate cortex Lateral occipital cortex, cuneus R 1574 2.75 0.00301 0.621 precuneus, cuneus, pericalcarine R 904 1.943 0.0425 0.561 region, isthmus of the cingulate cortex

Supplementary Table 3: Clusters with Significant Increase in GWPC in ASD Patients. The number of resolution elements corresponds to ​ the number of independent observations within the cluster. Hsph = Hemisphere, L = Left, R = Right

Supplementary figure 1 : Map of the difference in GWPC in ASD patients compared with control subjects with inclusion of estimated motion as covariate in the linear model (GMI measured at 30% cortical thickness). Only significant results at 5% after correction for ​ multiple RFT tests are shown. From left to right: left hemisphere lateral and medial view, right hemisphere lateral and medial view

2 Main cortical region Hemisphere Number of vertex Surface (mm )​ Cluster corrected Mean difference ​ points p-value (%)

lateral occipital Left 1631 1332.30 0.00020 0.4962

pericalcarine Left 1118 602.02 0.00080 0.4448

superior temporal Left 1183 496.43 0.00539 0.5611

precentral Left 1034 433.18 0.01316 0.6525

precentral Left 955 406.64 0.02010 0.5613

lateral occipital Right 770 624.82 0.00020 0.5021

precuneus Right 1019 507.36 0.00120 0.5077

precentral Right 1152 426.14 0.00699 0.5364

precentral Right 747 333.91 0.03921 0.6133

Supplementary Table 4: Clusters with Significant Increase in GWPC in ASD Patients with inclusion of cortical thickness as a covariate of the linear model (GMI measured at 30% cortical thickness). The number of resolution elements corresponds to the number of ​ independent observations within the cluster.

Differences between females and males

30%

40%

50%

60%

-1,50 -0,50 0 0,50 1,50 ​ GWPC difference (in%)

Supplementary Figure 2: Map of the difference in GWPC among females compared with males with inclusion of cortical thickness as a ​ ​ covariate of the linear model. Only the significant results at 5% after correction for multiple tests by Monte Carlo are represented. From ​ top to bottom: 30% to 60% GM depth taken into account in the calculation of the GWPC. Note that the colour scale used is similar to that of female's GWPC difference maps compared with male without inclusion of cortical thickness, in order to facilitate visual comparison.

-0,1 0 0,1 Cortical thickness difference (in mm) Supplementary Figure 3 : Map of cortical thickness differences among females compared with males. Only significant results at 5% after ​ correction by RFT for multiple tests are shown. From left to right: left hemisphere lateral and medial view, right hemisphere lateral and medial view

Cortical regions Hemisphe Number Number Cluster Mean re of vertex of corrected difference points resolution p-value (%) éléments insula, pre- and postcentral gyri, lateral orbitofrontal Left 8378 15.108 <1e-100 -0.912 cortex, pars orbitalis and opercularis of the inferior frontal gyrus, supramarginal gyrus, superior temporal gyrus Lateral occipital cortex, middle and lower temporal gyrus, Left 4841 10.52 2.35e-14 -0.768 cuneus, pericalcarine region, lower parietal cortex Medial and lateral orbitofrontal cortex, rostral portion of Left 3087 6.142 4.2e-08 -0.809 the middle frontal gyrus, pars orbitalis of the inferior frontal gyrus, frontal pole, superior frontal cortex, pars triangularis of the inferior frontal gyrus Lingual cortex, isthmus of the cingulate cortex, precuneus, Left 1900 4.932 2.24e-06 -0.819 parahippocampal gyrus Supramarginal gyrus, superior temporal gyrus Left 1380 3.199 0.000666 -0.797 precuneus, superior parietal gyrus Left 1152 2.272 0.014 -0.753 Fusiform cortex Left 966 2.258 0.0146 -0.679 lingual, cuneus, pericalcarine, isthmus of the cingulate Right 3589 10.423 3.24e-14 -0.815 cortex, parahippocampal, precuneus, lateral occipital insula, precentral, pars opercularis, postcentral, superior Right 5648 10.036 1.16e-13 -0.98 temporal, lateral orbitofrontal middle temporal, inferior parietal, inferior temporal, lateral Right 2133 4.752 4.03e-06 -0.863 occipital, Banks of the Superior Temporal Sulcus caudal anterior cingulate, posterior cingulate, rostral Right 1411 4.746 4.11e-06 -0.776 anterior cingulate rostral middle frontal, frontal pole, superior frontal, pars Right 2498 4.568 7.39e-06 -0.802 orbitalis, medial orbitofrontal fusiform, inferior temporal Right 1387 3.572 0.000195 -0.773 medial orbitofrontal Right 864 3.564 0.0002 -0.921

Supplementary Table 5: Clusters with statistically significant decrease in GWPC among females at 30% depth of GM. The number of ​ resolution elements corresponds to the number of independent observations within the cluster. P cluster is the p corrected value of the cluster

Differences with age

-0,3 0 0,3 GWPC difference per year (in%) Supplementary Figure 4: Map of the difference in GWPC with increasing age, with inclusion of cortical thickness as a covariate of the ​ ​ linear model (GMI measured at 30% of cortical thickness). Only significant results at 5% after correction by Monte Carlo for multiple tests ​ are shown). From left to right: left hemisphere lateral and medial view, right hemisphere lateral and medial view. Note that the colour scale used is similar to that of GWPC difference maps with increasing age without inclusion of the cortical thickness, in order to facilitate visual comparison.

-0,02 0 0,02 Difference in cortical thickness per year (in mm) Supplementary Figure 5: Map of cortical thickness differences with increasing age. Only significant results at 5% after correction by RFT ​ for multiple tests are shown). From left to right: left hemisphere lateral and medial view, right hemisphere lateral and medial view

Cortical regions Hemisphere Number of Number of Cluster Mean vertex resolution corrected difference points éléments p-value (%) Upper and middle frontal cortex, pre- and postcentral Left <1e-100 130433 306.637 -0.133 gyri, superior and inferior parietal cortex, supramarginal gyrus, precuneus, rostral middle frontal cortex, lateral occipital cortex, superior, middle, inferior and transverse temporal gyri, lingual cortex, paracentral sulcus, pars opercularis, fusiform cortex, posterior and anterior cingulate cortex, lateral and medial orbitofrontal cortex, superior temporal sulcus, isthmus of cingulate cortex, pars triangularis, insula, pericalcarine region, cuneus, pars orbitalis, frontal pole Temporal pole, entorhinal cortex, fusiform cortex, Left <1e-100 1675 14.561 0.067 upper and lower temporal gyri

Insula Left 1262 2.418 0.00865 0.066

Upper and middle caudal frontal cortex, pre- and Right <1e-100 130533 302.551 -0.134 postcentral gyri, paracentral sulcus, superior and inferior parietal cortex, supramarginal gyrus, precuneus, middle frontal cortex, latero-occipital cortex, superior, middle, inferior and transverse temporal gyri, lingual cortex, lateral and medial orbitofrontal cortex, posterior and anterior cingulate cortex, fusiform gyrus, pars opercularis, pars triangularis, superior temporal sulcus, isthmus of the cingulate cortex, pericalcarine region, cuneus, insula, pars orbitalis, frontal pole, parahippocampal cortex Temporal pole, parahippocampal cortex, entorhinal Right <1e-100 2491 14.452 0.055 cortex, fusiform gyrus, upper and middle temporal gyri, insula Insula Right 1428 2.424 0.00846 0.066

Medial orbito-frontal cortex Right 319 2.247 0.0151 0.064

Supplementary Table 6: Clusters with significant decrease in GWPC with age at 30% depth of GM. The number of resolution elements ​ corresponds to the number of independent observations within the cluster. P cluster is the p corrected value of the cluster

Distribution of GWPC among subjects

Supplementary figure 6: Distribution of mean GWPC for ASD patients and controls groups in the left occipital cluster. GWPC values are ​ corrected for age, sex and site effects.