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Objective: To develop effective methods for GWAS in admixed populations such as African Americans. Methods: We show that, when testing the null hypothesis that the test SNP is not in background linkage disequilibrium with the causal variants, several existing methods cannot control well the family-wise error rate (FWER) in the strong sense in GWAS. These existing methods include association tests adjusting for global ancestry and joint association tests that combine statistics from admixture mapping tests and association tests that correct for local ancestry. Furthermore, we describe a generalized sequential Bonferroni (smooth-GSB) procedure for GWAS that incorporates smoothed weights calculated from admixture mapping tests into association tests that correct for local ancestry. We have applied the smooth-GSB procedure to analyses of GWAS data on American Africans from the Atherosclerosis Risk in Communities (ARIC) Study. Results: Our simulation studies indicate that the smooth-GSB procedure not only control the FWER, but also improves statistical power compared with association tests correcting for local ancestry. Conclusion: The smooth-GSB procedure can result in a better performance than several existing methods for GWAS in admixed populations. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using serial data from the Fels Longitudinal Study, we investigated the effects of early and late attainment of the peak height velocity (PHV) in childhood on the timing of the appearance of the metabolic syndrome later in life. We aimed to show if early attainment of PHV engenders greater risks for chronic diseases in boys than in girls. Therefore, we defined those boys and girls in sex-specific quartiles of the study population that were slowest to attain PHV as having a slow tempo of development, and those in the growth that most rapidly attained PHV as having a rapid tempo of development. Boys who experienced an early onset of PHV tended to have a higher risk for the metabolic syndrome, dyslipidemia and impaired fasting glucose than those who had late onset of PHV. Girls who had an early onset of PHV tended to develop more abdominal obesity than females who had a late onset of PHV. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: For genome-wide association studies (GWAS) using case-control data with stratification, a commonly used association test is the generalized Armitage (GA) trend test implemented in the software EIGENSTRAT. The GA trend test uses principal component analysis to correct for population stratification. It usually assumes an additive disease model and can have high power when the underlying disease model is additive or multiplicative, but may have relatively low power when the underlying disease model is recessive or dominant. The purpose of this paper is to provide a test procedure for GWAS with increased power over the GA trend test under the recessive and dominant models, while maintaining the power of the GA trend test under the additive and multiplicative models. Methods: We extend a Hardy-Weinberg disequilibrium (HWD) trend test for a homogeneous population to account for population stratification, and then propose a robust association test procedure for GWAS that incorporates information from the extended HWD trend test into the GA trend test. Results and Conclusions: Our simulation studies and application of our method to a GWAS data set indicate that our proposed method can achieve the purpose described above. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Body composition during puberty is a marker of metabolic changes that occur during this period of growth and maturation, and, thus, holds key information regarding current and future health. During puberty, the main components of body composition (total body fat, lean body mass, bone mineral content) all increase, but considerable sexual dimorphism exists. Methods for measuring body composition (e.g. densitometry and dual-energy X-ray absorptiometry) and degree of maturity will be discussed in this review. Components of body composition show age-to-age correlations (i.e. ‘tracking’), especially from adolescence onwards. Furthermore, adipose tissue is endocrinologically active and is centrally involved in the interaction between adipocytokines, insulin and sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes. In conclusion, pubertal body composition is important, not only for the assessment of contemporaneous nutritional status, but also for being linked directly to the possible onset of chronic disease later in life and is, therefore, useful for disease risk assessment and intervention early in life.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]