Uncovering Local Trends in Genetic Effects of Multiple Phenotypes via Functional Linear Models.

Recent technological advances equipped researchers with capabilities that go beyond traditional genotyping of loci known to be polymorphic in a general population. Genetic sequences of study participants can now be assessed directly. This capability removed technology-driven bias toward scoring predominantly common polymorphisms and let researchers reveal a wealth of rare and sample-specific variants. Although the relative contributions of rare and common polymorphisms to trait variation are being debated, researchers are faced with the need for new statistical tools for simultaneous evaluation of all variants within a region. Several research groups demonstrated flexibility and good statistical power of the functional linear model approach. In this work we extend previous developments to allow inclusion of multiple traits and adjustment for additional covariates. Our functional approach is unique in that it provides a nuanced depiction of effects and interactions for the variables in the model by representing them as curves varying over a genetic region. We demonstrate flexibility and competitive power of our approach by contrasting its performance with commonly used statistical tools and illustrate its potential for discovery and characterization of genetic architecture of complex traits using sequencing data from the Dallas Heart Study.

Epidemiological evidence on count processes in the formation of tobacco dependence.

INTRODUCTION: Large-sample epidemiological studies of tobacco cigarette smoking routinely assess so-called "lifetime prevalence" of tobacco dependence. This work delves into the earliest stages of smoking involvement, focusing on newly incident tobacco cigarette smokers in the very recent past, and examines hypothesized subgroup variation in count processes that become engaged once smoking starts. Here, the term "count process" has two components: (a) whether smoking will be persistent and (b) the rate of smoking, conditional upon membership in a latent class of smokers who will persist, as estimated under the zero-inflated Poisson (ZIP) model for complex survey data. METHODS: We estimate these ZIP parameters for nationally representative samples of newly incident smokers in the United States (all with smoking initiation within 24 months of assessment). Data are from the 2004-2007 National Surveys on Drug Use and Health. RESULTS: Once cigarette smoking started, roughly 40%-45% persisted, and the estimated median rate was five smoking days/30 days, conditional on membership in the latent class of persistent smokers. Among non-Hispanic recent-onset cigarette smokers, Whites, Black/African Americans, Asians, and Native American/Alaskan Natives did not differ, but recent-onset smokers of Hispanic origin and those of Pacific Islander background had comparatively less cigarette involvement. DISCUSSION: Tobacco prevention and control initiatives may require elaboration in the form of brief interventions, including interpersonal and social transactions that might constrain a mounting frequency of days of smoking before daily smoking starts, and until conventional smoking cessation medication aids become indicated. These very-early stage interventions (VESI) might be mounted within family or peer groups or in the primary care or school settings, but randomized trials to evaluate VESI interventions will be required.

Comparison of cross-sectional geometry of the proximal femur in white and black women from Detroit and Johannesburg.

UNLABELLED: There are known black-white differences in bone density measured by DXA but less is known about bone architecture. We compared cross-sectional geometric properties of the proximal femur in U.S. black (n = 86) and white (n = 151) and South African black (n = 60) and white (n = 48) postmenopausal women. Results are consistent with greater bone strength in the black groups in both countries. INTRODUCTION: There are well-known ethnic differences in bone density, but little is known about ethnic differences in bone architecture between U.S. and South African blacks and whites. MATERIALS AND METHODS: We compared bone density and cross-sectional geometric properties of the proximal femur in 237 U.S. black (n = 86) and white (n = 151) and 108 South African black (n = 60) and white (n = 48) postmenopausal women. The proximal femur (neck, intertrochanteric region, and proximal shaft regions of interest) was measured with DXA and further analyzed with a hip structural analysis program. For each region, BMD, cross-sectional area, outer diameter, section modulus, endosteal diameter, average cortical thickness, and the buckling ratio were estimated. RESULTS AND CONCLUSIONS: In the femoral neck, in both countries, the blacks had narrower endosteal diameters (mean difference, 2.6% and 5.1% in U.S. and South African women, respectively), thicker cortices (9.3% and 11.0%), and a lower buckling ratio (11.6% and 15.2%) despite a similar outer diameter. In the intertrochanteric region, the whites had a greater outer diameter (2.2% and 3.0% in U.S. and South African women, respectively), lower cross-sectional area (4.8% and 7.2%), and a higher buckling ratio (7.6% and 3.6%). There are fewer differences in the shaft. Compared with South African whites, U.S. whites had wider (mean difference 2.9%) femoral necks and a greater section modulus (6.4%) in the shaft. U.S. whites also had greater cross-sectional area in both the neck and shaft (5.2% and 4.6%, respectively). The U.S. blacks had significantly greater outer diameters, cross-sectional areas, endosteal diameters, and section moduli in the neck region compared with South African blacks. Our observations are consistent with greater bone strength in the black groups in both countries, and they also suggest that there are fewer differences between the same ethnic groups in the two countries than there are between different ethnic groups within a country.

Radiographic measurements, bone mineral density, and the Singh Index in the proximal femur of white and black postmenopausal women.

BACKGROUND: Radiographic measurements, bone mineral density (BMD), and the Singh Index were examined to assess ethnic differences in the architecture and trabecular patterns in the proximal femur. METHODS: We measured height (cm), weight (kg), and the following radiographic variables in 326 white and black postmenopausal women participating in the Women's Health Initiative at the Clinical Center in Detroit, MI: neck breadth, inferior neck cortical thickness, head diameter, subtrochanteric breadth, and subtrochanteric medial and lateral cortical thicknesses. Bone densitometry was performed by dual-energy x-ray absorptiometry (Hologic QDR 1000 plus; Hologic Inc, Bedford, MA) at 5 regional sites in the proximal femur. The Singh Index was read by its originator. RESULTS AND CONCLUSIONS: There was no significant ethnic difference in mean age, height, or body mass index, but weight and BMD was higher in the black group at all regional sites. The inferior neck cortical thickness was significantly greater in the black group. The Singh Index was found to be grade VI (normal) in 87%, grade V in 9%, and grades II-IV in 4% of all subjects. Multiple regression models explained 35% to 60% of the variance in the regional BMDs; the Singh Index, weight, and subtrochanteric cortical thicknesses were significant contributors to all regional hip BMD models. Although there were ethnic differences in BMD, there were no ethnic differences in the distribution of the Singh Index scores.

An updated global picture of cigarette smoking persistence among adults.

BACKGROUND: Cross-national variance in smoking prevalence is relatively well documented. The aim of this study is to estimate levels of smoking persistence across 21 countries with a hypothesized inverse relationship between country income level and smoking persistence. METHODS: Data from the World Health Organization World Mental Health Survey Initiative were used to estimate cross-national differences in smoking persistence--the proportion of adults who started to smoke and persisted in smoking by the date of the survey. RESULTS: There is large variation in smoking persistence from 25% (Nigeria) to 85% (China), with a random-effects meta-analytic summary estimate of 55% with considerable cross-national variation. (Cochran's heterogeneity Q statistic = 6845; p < 0.001). Meta-regressions indicated that observed differences are not attributable to differences in country's income level, age distribution of smokers, or how recent the onset of smoking began within each country. CONCLUSION: While smoking should remain an important public health issue in any country where smokers are present, this report identifies several countries with higher levels of smoking persistence (namely, China and India).

Alcohol consumption associated with collegiate American football pre-game festivities.

Internationally, sporting events represent a specific context in which heavy episodic drinking is common. The current study assessed determinants of heavy episodic drinking among tailgaters (i.e., individuals engaging in pre-game social festivities) prior to American football games at two large universities. A total of 466 individuals at two universities completed a short interview and provided a breathalyzer sample to estimate breath alcohol content (BrAC) during the tailgating window (150min prior to and 10min after the start of the game). The plurality of participants, 48.5% at the southeastern university (School1) and 58.8% at the midwestern university (School2), engaged in heavy episodic drinking. Only 54 individuals (11.6%) from the combined sample at both universities abstained from alcohol (confirmed via BrAC). In total, 40.2% of participants at School1 and 31.9% at School2 produced breath samples over the legal limit for driving (i.e., BrAC=0.08 or higher). In site-specific regression analyses, younger ages, males, and non-students at School1, and younger ages and non-game attendance at School2 were associated with self-reported heavy episodic drinking and higher levels of estimated BrAC (p<0.05). Given the widespread participation in heavy episodic drinking among both students and non-students in this sample, public health interventions should be implemented both on- and off-campus to promote safety and to discourage heavy episodic drinking at American football games and other high-profile sporting events.