Trans-ethnic meta-analysis of white blood cell phenotypes.

White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.

Association between Race, Household Income and Grip Strength in Middle- and Older-Aged Adults.

BACKGROUND: Poor grip strength is an indicator of frailty and a precursor to functional limitations. Although poor grip strength is more prevalent in older disabled African American women, little is known about the association between race and poverty-related disparities and grip strength in middle-aged men and women. METHODS: We examined the cross-sectional relationship between race, socioeconomic status as assessed by household income, and hand grip strength in men and women in the Healthy Aging in Neighborhoods of Diversity across the Life Span study. General linear models examined grip strength (maximum of two trials on both sides) by race and household income adjusted for age, weight, height, hand pain, education, insurance status, family income, and two or more chronic conditions. RESULTS: Of 2,091 adults, 422(45.4%) were male, 509(54.8%) were African American, and 320 (34.5%) were living in households with incomes below 125% of the federal poverty level (low SES). In adjusted models, African American women had greater grip strength than White women independent of SES (low income household: 29.3 vs 26.9 kg and high income household: 30.5 vs. 28.3kg; P<.05 for both); whereas in men, only African Americans in the high income household group had better grip strength than Whites (46.3 vs. 43.2; P<.05). CONCLUSIONS: The relationship between grip strength, race and SES as assessed by household income varied in this cohort. Efforts to develop grip strength norms and cut points that indicate frailty and sarcopenia may need to be race- and income-specific.

Genome-wide association study of age at menarche in African-American women.

African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single-nucleotide polymorphisms (SNPs) in a total of 18 089 AA women in 15 studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2850 women (Stage 2). First, while no SNP passed the pre-specified P < 5 × 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Secondly, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.