Faculty Bibliography

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.

Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD (aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health. We tested signals with P < 5 × 10(-6) for replication in an independent, same-age cohort of 486 Caucasian children. Two loci yielded a genome-wide significant combined P-value: rs7797976 within CPED1 in females [P = 2.4 × 10(-11), β =- 0.30 standard deviations (SD) per T allele; aBMD-Z] and rs7035284 at 9p21.3 in males (P = 1.2 × 10(-8), β = 0.28 SD per G allele; BMC-Z). Signals at the CPED1-WNT16-FAM3C locus have been previously associated with BMD at other skeletal sites in adults and children. Our result at the distal radius underscores the importance of this locus at multiple skeletal sites. The 9p21.3 locus is within a gene desert, with the nearest gene flanking each side being MIR31HG and MTAP, neither of which has been implicated in BMD or BMC previously. These findings suggest that genetic determinants of childhood bone accretion at the radius, a skeletal site that is primarily cortical bone, exist and also differ by sex.

We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study (n = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between an SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex • SNP interaction, revealing a significant association only in females (b = -0.32, p = 1.8 × 10(-6)). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 × 10(-5)). In contrast, the sex • SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, p = 4.4 × 10(-4)) and distal radius aBMD (b = 0.27, p = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex • SNP interactions were found at 15 loci; pubertal stage • SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation.

The objectives of the present study are to identify sociodemographic factors associated with father nurturance and assess the relationship between parental (mother and father) nurturance and youth psychological well-being among 216 African American college-aged youth. Participants attended a historically Black college in the Mid-Atlantic region. Findings indicated that the frequency and duration of the participants"™ interactions with their fathers were associated with levels of father nurturance. Youth whose mothers and fathers were married or cohabitating, compared with those who were separated, divorced, widowed, or never married, had lower levels of psychological well-being. Furthermore, youth who reported more mother nurturance had higher levels of overall psychological well-being. These findings highlight the importance of time-based variables in youths"™ perceptions of father nurturance and raise important questions about how the nature of the coparental relationship and variations in the fathering role affect youth well-being.

With the emergence of food allergy as an important public health problem, it has become clear that there is an unmet need in regard to treatment. In particular, IgE-mediated food allergy that is associated with risk of fatal anaphylaxis has been the subject of multiple studies in the past decade. The growing body of evidence derived from multiple centres and various study designs indicates that for IgE-mediated food allergy, immunomodulation through food immunotherapy is possible; however, the extent of protection afforded by such treatment is highly variable. At this time, the capacity for food immunotherapy to restore permanent tolerance to food has not been demonstrated conclusively. This review will discuss these topics as they apply to the most important studies of food oral immunotherapy.

OBJECTIVE:Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI. METHOD/METHODS:We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses. RESULTS:The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity. CONCLUSION/CONCLUSIONS:Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.

The majority of individuals working with justice-involved youth receive limited training addressing the impact of childhood trauma. There is a need for trauma-related training for staff, as well as valid measures to evaluate the effectiveness of training. The National Child Traumatic Stress Network designed a training curriculum, Think Trauma, which educates staff about the impact of trauma on justice-involved youth. A 45-item Think Trauma Evaluation Questionnaire (TTEQ) was developed to assess participants' changes in knowledge and attitudes. This article examines the factor structure and internal consistency of this questionnaire. Two-hundred and ninety-six employees at two secure juvenile detention centers completed the TTEQ. The results suggest that the questionnaire is feasible to administer to a large group and has a factor structure corresponding to areas covered in the curriculum. A reliable and valid measure of trauma knowledge and attitudes is important to identifying the training needs for a particular facility

Independent lines of research illustrate the benefits of social support and the negative consequences of conflict and emotional neglect across family and peer contexts with regard to depression. However, few studies have simultaneously examined negative and positive interactions across relationships. We sought to address this gap in the literature by utilizing a person-centered approach to a) understand empirical, interpersonal profiles in youth and b) understand how these profiles confer risk for prospective depression. At baseline, 678 youth (380 females; 298 males) 3rd (N = 208), 6th (N = 245), and 9th graders (N = 225) completed self-report measures for self-perceived negative/positive relationships across family and peers, anxiety symptoms, and depressive symptoms in a laboratory setting. Next, youth were called every 3 months for 18 months and completed self-report depressive and anxiety symptom forms. Two-step cluster analyses suggested that children and adolescents fell into one of three interpersonal clusters, labeled: Support, Conflict, and Neglect. Our analyses supported a convergence model in which the quality of relationship was consistent across peers and family. Furthermore, mixed-level modeling (MLM) findings demonstrated that youth in the Conflict cluster were at increased risk for prospective depressive symptoms, while the Supported and Neglected profiles demonstrated similar symptom levels. Findings were unique to depressive symptoms and consistent across sex and age. Conflict seemed to uniquely confer risk for depression as findings concerning anxiety were not significant. These findings influence our interpersonal conceptualization of depression as well as clinical implications for how to assess and treat depression in youth.