Table S1 Studies of OXTR polymorphisms associated with social and pathological behaviors in humansSNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs53576 Empathy 192 college

students (59% female) of mixed ethnicity

Compared with GG individuals, AA/AG individuals exhibited lower behavioral and dispositional empathy. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals

Rodrigues et al., 2009

rs53576 Empathy 1536 Chinese participants (710 female)

G allele carriers showed a stronger association between interdependence and empathy trait compared with A/A homozygotes

Luo et al., 2015

rs53576 Empathic concern

51 males aged 18-35 of mixed race

GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern

Smith et al., 2014

rs2268498 NegativeEmotionality

750 healthy young Caucasians (510 females)

Carriers of the 5-HTTLPR LL genotype in combination with the TT genotype of the OXTR rs2268498 showed lowest scores on Negative emotionality traits

Montag et al., 2011

15 tagging SNPs Depressive temperament

493 healthy Japanese subjects (186 females)

Haplotype GGGTGTC (rs11131149-rs2243370-rs2243369-rs13316193-rs2254298-rs2268493-rs2268491) is significantly associated with a lower depressive temperament score

Kawamura et al., 2010

rs53576 Emotional support seeking

134 young Koreans (63female) and 140 young Americans (79 females)

Among distressed American participants, those with the GG/AG genotypes reported seeking more emotional social support, compared with those with the AA genotype

Kim et al., 2010

rs53576rs1042778

Positive maternal parenting

A total 40 mothers and their children; African and European descent

Mothers with A alleles of rs53576 or T alleles of rs1042778 exhibited higher levels of positive parenting

Michalska et al., 2014

Table S1 ContinuedSNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs53576 Parenting 159 mothers with

their 2-year-old toddlers (Caucasian)

Mothers with AA/AG genotypes showed lower levels of sensitive responsiveness to their toddlers

Bakermans-Kranenburg and van Ijzendoorn, 2008

rs53576 Harm avoidance

324 healthy young adults (Chinese Han)

Female subjects with the AA genotype showed increased harm avoidance scores relative to G-carrier females

Wang et al., 2014

15 tagging SNPs Social decision making

The first sample consisting of 203 healthy young adults (101 female); A second sample consisting of 98 mothers. Ethnicity was not specified

rs1042778 was significantly associated with both the Dictator Game (DG) and the Social Values Orientation (SVO) task; individuals with GG+GT genotypes was more generous than individuals with TT genotypesThe 4 locus haplotype block (rs9840864-rs237888-rs2268490-rs237887) is significant for Dictator Giving, SVO (Risky alleles were not specified)

Israel et al., 2009

rs53576 Trust 108 healthy male students (European ancestry)

Individuals with GG genotype showed higher trust behavior than individuals with A allele carriers (AA/AG)

Krueger et al., 2012

rs53576 Prosocial temperament

309 participants of Caucasians of European ancestry

Homozygotes for the risk allele (AA) showed the lowest reward dependence (RD) values, whereas AG/GG carriers displayed intermediate and highest RD values, respectively

Tost et al., 2010

rs53576 Emotional sensitivity

128 white female undergraduate students

G carriers were more emotionally sensitive (lower self-esteem) in response to social ostracism (social stressor) relative to individuals with AA genotype

McQuaid et al., 2015

Table S1 ContinuedSNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs53576 Sympathetic

reactivity93 old-aged individuals; non-Hispanic White, Black, and non-Black Hispanic

G/G participants displayed significantly higher levels of sympathetic reactivity to psychological stress with G/G males showing the highest levels of sympathetic response to stress

Norman et al., 2012

rs53576 Psychological resourcesDepressive symptoms

326 individuals (199 female), 117 Asian ancestry, 87 Europeans or European-Americans, 49 Hispanic

Carriers of the “A” allele have lower levels of optimism, mastery, and self-esteem, relative to G/G homozygotes. A-allele carriers also had significantly greater levels of depressive symptomatology

Saphire-Bernstein et al., 2011

10 tagging SNPs Empathy 101 healthy young Chinese adults (55 females)

Participants with rs2268491 CT genotype/ rs2254298 CT genotype display more cognitive empathy than those with CC genotype/ TT genotype;Individuals with rs237887 A allele / rs4686302 T allele showed higher emotional empathy than those with G allele/ C allele

Wu et al., 2012

rs53576rs2254298rs2228485

Affect, loneliness and intelligence

289 adults (187 females), 117 adolescents (58 females)

Male individuals with the rs53576 A/A genotype showed lower positive affect scores;Haplotypes constructed with the three markers were associated with positive affect, negative affect and emotional Loneliness (Risky alleles were not specified)Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents

Lucht et al., 2009

rs53576rs2254298

Trait empathy 145 schizophrenic subjects and 145 healthy control subjects; ethnicity was not specified

Schizophrenic patients carrying rs2254298 one or two A-alleles showed significantly more ‘empathic concern’ than those carrying two G-alleles

Montag et al., 2012

Table S1 ContinuedSNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs75775, rs1488467, rs4564970, rs53576,rs237897, rs237887,rs11720238,rs4686302, rs2254298, rs2268493, rs1042778, rs7632287

Pair-bonding The first sample consisting of 2309 twin pairs and their spouses; the second sample consisting of 1240 participants in another center

Women carrying one or two copies of the rs7632287 A-allele scored lower on the measures indicative of pair-bonding scales than did women carrying two copies of the G-allele

Walum et al., 2012

60 tagging SNPs Social recognition skills

198 probands with autism; together with 393 family memebers, of which 62 were female. Ethnicity is not specified

rs237887 was strongly associated with recognition memory in combined probands, parents, and siblings. Homozygotes for the ancestral A allele had impairments irrespective of their diagnostic status.

Skuse et al., 2014

rs53576rs2254298

Depression 185 patients with major depression or bipolar disorders and 192 matched healthy controls. Ethnicity is not specified

The GG genotype of rs53576 and rs2254298 was positively associated with unipolar depression. In this group, GG individuals were also associated with high scores on Attachment Style Questionnaire factors and high levels of adult separation anxiety

Costa et al., 2009

rs2254298 Depression and anxiety

92 Caucasian adolescent girls

Heterozygous (AG) girls in the high-adversity group reported significantly higher symptom levels of depression, physical anxiety, and social anxiety than did participants in the other three groups (low-adversity AGs, low-adversity GGs and high-adversity GGs)

Thompson et al., 2011

Table S1 Continued

SNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs53576 Depression 441 youth (261

female) and 413 are Caucasian

Youth possessing at least one A allele who also had a history of maternal depression exhibited the highest levels of depressive symptoms at age 15

Thompson et al., 2014

rs53576 Depression 288 university students (213 females), ethnicity including White (n = 167), Black (n = 34), Asian (n = 23)

The G carriers reported greater severity of depressive symptoms when they reported high levels of maltreatment compared to those individuals with the AA genotype

McQuaid et al., 2013

rs53576 Stress 194 healthy male participants, most of them from European descent

Only individuals with one or two copies of the G allele showed lower cortisol responses to stress after social support, compared with individuals with the same genotype receiving no social support.

Chen et al., 2011a

rs2254298rs53576

Attachment 176 healthy infants (98 male, 77 Caucasian, 99 non-Caucasian)

The A allele of rs2254298 was associated with attachment security in the non-Caucasian infants

Chen et al.,2011b

rs53576rs2254298

Social impairments

79 children with ASD, 52 unaffected siblings, and 62 unrelated neurotypical control children

Carriers of the “G” allele of rs53576 showed impaired affect recognition performance and carriers of the “A” allele of rs2254298 exhibited greater global social impairments in all groups

Parker et al., 2014

rs2254298, rs53576, rs237901, rs2228485

Autism 195 Chinese Han family trios (21 females)

rs2254298 A, rs553576 A and haplotypes involving rs53576 were significantly associated with autism

Wu et al., 2005

Table S1 Continued

SNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs2254298,rs53576

Autism 57 Caucasian trios (12 females)

rs2254298 G was overtransmited in autism Jacob et al., 2007

22 tagging SNPs Autistic Disorders on High-Functioning Level

100 individuals (5 female) with ASD with high-functioning level

The rs2270465 G-allele is more frequently transmitted the autistic patients. SNPs of the marker combination (rs237851-rs6791619-rs53576-rs237884/ haplotype T-G-T-T) yielding the strongest evidence of association with ASD

Wermter et al., 2010

25 tagging SNPs Autism 5,432 individuals from 1,238 pedigrees including 2,333 individuals with ASD, 95% is Caucasian

The rs1042778 G allele, rs7632287 G allele and rs2268493 T allele were associated with ASD

Campbell et al., 2011

18 tagging SNPs Autism 152 subjects with ASDs (24 women) and their family members; Israeli individuals

The five-locus haplotype A-T-T-G-A (rs237897-rs13316193-rs237889-rs2254298-rs2268494) showed highly significantly association with ASD;rs1042778 G allele and rs2268494 A allele were also significantly associated with autistic disorder; rs2254298 G allele was associated with Vineland Adaptive Behavior Scale daily living skills and communication subdomain scores with G being the risk allele

Lerer et al.,2008

11 tagging SNPs Autism A set consisting of 223 subjects with ASDs and with their parents. Another set comprising 65 subjects with ASDs (8 females);

Single-marker association analysis showed four SNPs, including rs237887, rs2268491, rs2254298 and rs2268495 were significantly associated with ASD (ATAA)The five-SNP haplotype (rs918316, rs2268491, rs2268493, rs2254298 and rs11131149, TTTTAG) showed a significant association with ASD

Liu et al., 2010

Table S1 Continued

SNPs Trait Ethnicity Associated genotype or haplotype/ Behavioral phenotype Referencesrs237885, rs13316193, rs237995,rs6770632,rs53576

ADHD 450 ADHD probands and their parents (from the UK and Ireland)

The rs53576 AA genotype was associated with better social ability compared to the AG genotype. The rs13316193 CC genotype was significantly associated with poorer social ability than the TT genotype

Park et al., 2010

rs53576,rs237880, rs237885,rs237902

Schizophrenia 406 schizophrenic patients and 406 control subjects (European descent)

rs53576(AG) and rs237885(TT) being more common in the schizophrenia sample compared to controls.rs53587-rs237902 A-G haplotype was over-represented in the patient group compared to the healthy control groupHigher PANSS general scores in rs53576 GG- than in AA-genotype patientsHigher PANSS negative scores in rs237902 GG- than in AA-genotype patients

Montag et al., 2013

12 tagging SNPs Schizophrenia 140 schizophrenia patients (82%Caucasians)

Furthermore, variants in the OXTR were nominally associated with severity of overall symptoms (rs237885, rs237887) as well as on the improvement of the positive symptoms (rs11706648, rs4686301, rs237899); risky alleles were not specified

Souza et al., 2010

Abbreviation: ASD, autism spectrum disorder; PANSS, positive and negative syndrome scale.

Table S2 List of the 37 OXTR SNPs genotyped in the initial analysisSNP Position Major allele Minor allele MAFrs7634632 8754169 C T 0.49rs237884 8768584 C T 0.25rs11914885 8771402 A G 0.32rs237865 8773968 A C 0.40rs151462 8781607 C G 0.34rs237875 8782406 A G 0.45rs6791619 8788186 C T 0.49rs11720238 8791339 C T 0.14rs7632287 8791446 G A 0.25rs2270465 8791976 G C 0.43rs1042778 8794545 G T 0.39rs237885 8795543 G T 0.45rs11706648 8796547 A C 0.33rs237887 8797042 A G 0.42rs2268490 8797085 C T 0.12rs237888 8797095 T C 0.15rs918316 8798181 T C 0.07rs9840864 8798477 G C 0.23rs4686301 8798586 C T 0.33rs2268491 8800398 C T 0.10rs2268493 8800840 T C 0.28rs2268494 8802046 T A 0.09rs2254298 8802228 G A 0.11rs237889 8802483 C T 0.40rs13316193 8802743 T C 0.38rs11131149 8802851 G A 0.37rs2268495 8807535 G A 0.25rs237897 8808285 G A 0.37rs237899 8808515 G A 0.39rs237902 8809184 G A 0.39rs4686302 8809222 C T 0.12rs2228485 8809703 A G 0.26rs4564970 8810408 T C 0.07rs2268498 8812411 T C 0.46rs1488467 8813231 T C 0.05rs75775 8820732 C T 0.15rs237851 8834723 G A 0.49

Abbreviation: MAF, minor allele frequency.Note: The SNPs with the regular font were excluded due to having a MAF below 0.1 or being in high linkage disequilibrium with other SNP in the sample (D' = 1, we kept the one which has

been suggested as a more promising candidate). The 10 SNPs with the bold font were in the final analysis in the present study.

Figure S1Figure S1. A Allele carriers (AA/AG) of OXTR rs2254298 had significantly lower rs-fMRI DMN signal synchronicity in bilateral fronto-insular cortex, putamen and globus pallidus, dACC, right dorsolateral prefrontal cortex and left caudate nucleus, compared to individuals with GG genotype by using more lenient statistical thresholds (min Z > 2.3; cluster significance: p < 0.05, two-tailed; Gaussian random field theory correction).