sj-docx-1-jiv-10.1177_08862605231198245 – Supplemental material for Childhood Emotional Neglect and Cognitive Function Among Middle-Aged and Older Adults: Mediating Role of Social Engagement

Supplemental material, sj-docx-1-jiv-10.1177_08862605231198245 for Childhood Emotional Neglect and Cognitive Function Among Middle-Aged and Older Adults: Mediating Role of Social Engagement by Weiwei Wang, Xinger Xia and Huiping Zhang in Journal of Interpersonal Violence</p

Characterization from Preparation of Cu-ZSM-5 catalysts by chemical vapour deposition for catalytic wet peroxide oxidation of phenol in a fixed bed reactor

TGA profiles ，N2 adsorption–desorption isotherms of the samples ，Elemental analysis results ，H2 temperature-programmed reduction profile

Characterization from Preparation of Cu-ZSM-5 catalysts by chemical vapour deposition for catalytic wet peroxide oxidation of phenol in a fixed bed reactor

TGA profiles ，N2 adsorption–desorption isotherms of the samples ，Elemental analysis results ，H2 temperature-programmed reduction profile

Identification of <em>POMC</em> Exonic Variants Associated with Substance Dependence and Body Mass Index

<div><h3>Background</h3><p>Risk of substance dependence (SD) and obesity has been linked to the function of melanocortin peptides encoded by the proopiomelanocortin gene (<em>POMC</em>).</p> <h3>Methods and Results</h3><p><em>POMC</em> exons were Sanger sequenced in 280 African Americans (AAs) and 308 European Americans (EAs). Among them, 311 (167 AAs and 114 EAs) were affected with substance (alcohol, cocaine, opioid and/or marijuana) dependence and 277 (113 AAs and164 EAs) were screened controls. We identified 23 variants, including two common polymorphisms (rs10654394 and rs1042571) and 21 rare variants; 12 of which were novel. We used logistic regression to analyze the association between the two common variants and SD or body mass index (BMI), with sex, age, and ancestry proportion as covariates. The common variant rs1042571 in the 3′UTR was significantly associated with BMI in EAs (Overweight: <em>P</em>_adj = 0.005; Obese: <em>P</em>_adj = 0.018; Overweight+Obese: <em>P</em>_adj = 0.002) but not in AAs. The common variant, rs10654394, was not associated with BMI and neither common variant was associated with SD in either population. To evaluate the association between the rare variants and SD or BMI, we collapsed rare variants and tested their prevalence using Fisher’s exact test. In AAs, rare variants were nominally associated with SD overall and with specific SD traits (SD: <em>P</em>_FET,1df = 0.026; alcohol dependence: <em>P</em>_FET,1df = 0.027; cocaine dependence: <em>P</em>_FET,1df = 0.007; marijuana dependence: <em>P</em>_FET,1df = 0.050) (the <em>P</em>-value from cocaine dependence analysis survived Bonferroni correction). There was no such effect in EAs. Although the frequency of the rare variants did not differ significantly between the normal-weight group and the overweight or obese group in either population, certain rare exonic variants occurred only in overweight or obese subjects without SD.</p> <h3>Conclusion</h3><p>These findings suggest that <em>POMC</em> exonic variants may influence risk for both SD and elevated BMI, in a population-specific manner. However, common and rare variants in this gene may exert different effects on these two phenotypes.</p> </div

Functional prediction of identified <i>POMC</i> rare variants.

<p>5′ UTR: transcription factors (TFs) were queried using DNA sequences harboring variants in the 5′ untranslated regions (5' UTRs) against the Transcription Element Search System.</p><p>Coding Region: potential functional and structural changes caused by missense variants in coding regions were predicted by the program PolyPhen.</p><p>3' UTR: microRNAs targeting 3′ untranslated region (3' UTR) sequences containing variants were predicted by program TargetScan, and changes in minimal free energy (mfe) due to mutations are presented in parentheses.</p><p>PhyloP score or evolutionary conservation score: calculated by the program PhyloP, which is built into the UCSC genome browser based on multiple alignments of 46 vertebrate species.</p

Scatter plots of subjects with rare variants according to substance dependence (SD) and BMI.

<p>Each rhombus represents a subject with a rare variant. Each row across the Y axis represents one type of rare variants. The X-axis represents two major groups: cases with substance dependence (SD) (on right side) and controls (on left side). Within each group, subjects carrying rare variants are divided into three groups according to BMI scores: the normal-weight group (BMI: 18.5–24.9), the over-weight group (BMI: 25–29.9), and the obese group (BMI ≥30). Overweight control subjects are represented with dark rhombuses and normal weight SD cases are represented with grey rhombuses.</p

Common and rare variants identified in <i>POMC</i> exons.

<p>SD: substance (alcohol, cocaine, opioid and/or marijuana) dependence.</p><p>AAs: African Americans; EAs: European Americans.</p><p>MAF: minor allele frequency.</p><p>n/N: number of rare variants (n)/number of total chromosomes (N).</p

Characteristics of case and control subjects.

<p>SD: substance (alcohol, cocaine, opioid and/or marijuana) dependence.</p><p>AD: alcohol dependence; CD: cocaine dependence; OD: opiate dependence; MjD: marijuana dependence.</p><p>BMI: body mass index (kg/m²).</p

Schematic genomic structure of <i>POMC</i> and locations of identified variants.

<p>Asterisk “*” indicates that the variant was newly identified.</p

Collapse association of <i>POMC</i> rare variants with substance dependence (SD) or body mass index (BMI).

<p>SD: substance (alcohol, cocaine, opioid and/or marijuana) dependence.</p><p>AD: alcohol dependence; CD: cocaine dependence; OD: opioid dependence; MjD: marijuana dependence.</p><p>Normal weight: BMI  = 18.5–24.9; Overweight: BMI  = 25–29.9; Obese: BMI ≥30;</p><p><i>P</i>_FET,_1df: <i>P</i> values obtained using the rare variant collapsing method and the Fisher Exact test (df  = 1).</p><p>Counts: adjusted numbers of minor (before the slash symbol "/") and total (after the slash symbol "/") alleles in the conditioned group (i.e., subjects with SD or high BMI, on the left side) and the comparison group (i.e., control subjects or subjects with normal BMI, on the right side) using the harmonic mean method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045300#pone.0045300-Xie2" target="_blank">[42]</a>.</p