X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

• MeSH
• Androgens * genetics   MeSH
• Genome-Wide Association Study * MeSH
• Genetic Predisposition to Disease MeSH
• Polymorphism, Single Nucleotide MeSH
• Kidney MeSH
• Humans MeSH
• Chromosomes, Human, X genetics   MeSH
• Response Elements MeSH
• Tetraspanins genetics   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

INTRODUCTION: African Americans, especially those in the South, suffer a disproportionate burden of obesity and are at high risk for perceived discrimination (PD). This study investigates the association between PD and weight status among African Americans and clarifies the role of perceived stress and health behaviors in this relationship. METHODS: Data came from the Jackson Heart Study, Examination 1 (2000-2004; analyses conducted in 2016 using Stata, version 14). African Americans from Jackson, Mississippi, aged 21-95 years were recruited (N=5,301). Weight status was measured using anthropometric data with BMI; waist circumference (in centimeters); and obesity class (I, II, III). Survey instruments were used to measure PD, perceived global stress, and health behaviors. Multivariate regression was used to model weight status outcomes as a function of PD, perceived stress, and health behaviors. RESULTS: After controlling for sociodemographic factors and health status, perceived everyday discrimination was associated with higher BMI (b=0.33, p<0.01); higher waist circumference (b=0.70, p<0.01); and higher relative risk of Class III obesity versus non-obesity (relative risk ratio, 1.18; p<0.001). Global perceived stress was linked to higher BMI (b=0.42, p<0.05) and higher waist circumference (b=1.18; p<0.01) and partially mediated the relationships between PD and these weight status outcomes. Health behaviors led to suppression rather than mediation between PD and weight status and between stress and weight status. CONCLUSIONS: PD and perceived stress are potential risk factors for higher weight status. They should be considered as a part of a comprehensive approach to reduce obesity among African Americans.

• MeSH
• Black or African American psychology   MeSH
• Discrimination, Psychological * MeSH
• Adult MeSH
• Body Mass Index MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Obesity epidemiology   psychology   MeSH
• Waist Circumference MeSH
• Cost of Illness MeSH
• Perception * MeSH
• Surveys and Questionnaires MeSH
• Stress, Psychological psychology   MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Health Behavior * MeSH
• Health Status MeSH
• Life Style MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Mississippi epidemiology   MeSH