Kimberly D. Williams

Landscape Genetics Reveals Focal Transmission of a Human Macroparasite

Macroparasite infections (e.g., helminths) remain a major human health concern. However, assessing transmission dynamics is problematic because the direct observation of macroparasite dispersal among hosts is not possible. We used a novel landscape genetics approach to examine transmission of the human roundworm Ascaris lumbricoides in a small human population in Jiri, Nepal. Unexpectedly, we found significant genetic structuring of parasites, indicating the presence of multiple transmission foci within a small sampling area (∼14 km2). We analyzed several epidemiological variables, and found that transmission is spatially autocorrelated around households and that transmission foci are stable over time despite extensive human movement. These results would not have been obtainable via a traditional epidemiological study based on worm counts alone. Our data refute the assumption that a single host population corresponds to a single parasite transmission unit, an assumption implicit in many classic models of macroparasite transmission. Newer models have shown that the metapopulation-like pattern observed in our data can adversely affect targeted control strategies aimed at community-wide impacts. Furthermore, the observed metapopulation structure and local mating patterns generate an excess of homozygotes that can accelerate the spread of recessive traits such as drug resistance. Our study illustrates how molecular analyses complement traditional epidemiological information in providing a better understanding of parasite transmission. Similar landscape genetic approaches in other macroparasite systems will be warranted if an accurate depiction of the transmission process is to be used to inform effective control strategies.

Genetic analysis of self-reported physical activity and adiposity: the Southwest Ohio Family Study.

OBJECTIVE Physical inactivity poses a major risk for obesity and chronic disease, and is influenced by both genetic and environmental factors. However, the genetic association between physical activity (PA) level and obesity is not well characterized. Our aims were to: (i) estimate the extent of additive genetic influences on physical activity while adjusting for household effects; and (ii) determine whether physical activity and adiposity measures share common genetic effects. SUBJECTS The sample included 521 (42 % male) adult relatives, 18-86 years of age, from five large families in the Southwest Ohio Family Study. DESIGN Sport, leisure and work PA were self-reported (Baecke Questionnaire of Habitual Physical Activity). Total body and trunk adiposity, including percentage body fat (%BF), were measured using dual-energy X-ray absorptiometry. Abdominal visceral and subcutaneous adipose tissue mass were measured using MRI. RESULTS Heritabilities for adiposity and PA traits, and the genetic, household and environmental correlations among them, were estimated using maximum likelihood variance components methods. Significant genetic effects (P < 0.05) were found for sport (h2 = 0.26) and leisure PA (h2 = 0.17). Significant (P < 0.05) household effects existed for leisure PA (c2 = 0.25). Sport PA had a negative genetic correlation with central adiposity measurements adjusted for height (rhoG > |-0.40|). Sport and leisure PA had negative genetic correlations with %BF (rhoG > |-0.46|). CONCLUSIONS The results suggest that the association of sport and leisure PA with lower adiposity is due, in part, to a common genetic inheritance of both reduced adiposity and the predisposition to engage in more physical activity.

Host genetics and population structure effects on parasitic disease.

Host genetic factors exert significant influences on differential susceptibility to many infectious diseases. In addition, population structure of both host and parasite may influence disease distribution patterns. In this study, we assess the effects of population structure on infectious disease in two populations in which host genetic factors influencing susceptibility to parasitic disease have been extensively studied. The first population is the Jirel population of eastern Nepal that has been the subject of research on the determinants of differential susceptibility to soil-transmitted helminth infections. The second group is a Brazilian population residing in an area endemic for Trypanosoma cruzi infection that has been assessed for genetic influences on differential disease progression in Chagas disease. For measures of Ascaris worm burden, within-population host genetic effects are generally more important than host population structure factors in determining patterns of infectious disease. No significant influences of population structure on measures associated with progression of cardiac disease in individuals who were seropositive for T. cruzi infection were found.

Evaluation of Qualitative Methods for Phenotyping Brachymesophalangia - V from Radiographs of Children

Objective: Brachymesophalangia‐V (BMP‐V), the general term for a short and broad middle phalanx of the 5th digit, presents both alone and in a large number of complex brachydactylies and developmental disorders. Past anthropological and epidemiological studies of growth and development have examined the prevalence of BMP‐V because small developmental disorders may signal more complex disruptions of skeletal growth and development. Historically, however, consensus on qualitative phenotype methodology has not been established. In large‐scale, non‐clinical studies such as the Fels Longitudinal Study and the Jiri Growth Study, quantitative assessment of the hand is not always the most efficient manner of screening for skeletal dysmorphologies. The current study evaluates qualitative phenotyping techniques for BMP‐V used in past anthropological studies of growth and development to establish a useful and reliable screening method for large study samples.

Heritability of brachydactyly type A3 in children, adolescents, and young adults from an endogamous population in eastern Nepal.

ABSTRACT Brachymesophalangia-V (BMP-V), a short and broad middle phalanx of the fifth digit, is the most common of all skeletal anomalies of the hand. When this feature appears alone, it is clinically known as brachydactyly type A3 (BDA3). A high prevalence of BDA3 has been observed among the children of the Jirel ethnic group in eastern Nepal. As part of the Jiri Growth Study, a hand-wrist radiograph is taken annually of each child to assess skeletal development. For this study the most recent radiographs of 1,357 Jirel children, adolescents, and young adults (676 boys, 681 girls), age 3–20 years, were examined for the presence or absence of BDA3, to report the prevalence and estimate the heritability of BDA3 in the Jirel population. The overall prevalence of BDA3 in this sample was 10.5% (12.9% of the males and 8.9% of the females were classified as BDA3 affected). The additive genetic heritability of BDA3 was statistically significant in this sample (h2 ± SE = 0.87 ± 0.16, p < 0.0001). This study is the first to estimate the prevalence and heritability of BDA3 in a large South Asian family-based sample.

Genome-wide linkage scan for quantitative trait loci underlying normal variation in heel bone ultrasound measures.

Quantitative ultrasound (QUS) traits are correlated with bone mineral density (BMD), but predict risk for future fracture independent of BMD. Only a few studies, however, have sought to identify specific genes influencing calcaneal QUS measures. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing normal variation in QUS traits. QUS measures were collected from a total of 719 individuals (336 males and 383 females) from the Fels Longitudinal Study who have been genotyped and have at least one set of QUS measurements. Participants ranged in age from 18.0 to 96.6 years and were distributed across 110 nuclear and extended families. Using the Sahara ® bone sonometer, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI) were collected from the right heel. Variance components based linkage analysis was performed on the three traits using 400 polymorphic short tandem repeat (STR) markers spaced approximately 10 cM apart across the autosomes to identify QTL influencing the QUS traits. Age, sex, and other significant covariates were simultaneously adjusted. Heritability estimates (h2) for the QUS traits ranged from 0.42 to 0.57. Significant evidence for a QTL influencing BUA was found on chromosome 11p15 near marker D11S902 (LOD = 3.11). Our results provide additional evidence for a QTL on chromosome 11p that harbors a potential candidate gene(s) related to BUA and bone metabolism.

Nonsyndromic Brachydactyly Type D and Type E Mapped to 7p15 in Healthy Children and Adults from the Jirel Ethnic Group in Eastern Nepal

There is phenotypic overlap between Brachydactyly Type D (BDD) and Brachydactyly Type E (BDE) that suggests a possible common underlying etiology. We seek to understand the genetic underpinnings of, and relationship between, these skeletal anomalies.

Presentation, Heritability, and Genome-Wide Linkage Analysis of the Midchildhood Growth Spurt in Healthy Children from the Fels Longitudinal Study

Abstract Growth is a complex process composed of distinct phases over the course of childhood. Although the pubertal growth spurt has received the most attention from auxologists and pediatricians, the midchildhood growth spurt has been less well studied. The midchildhood growth spurt refers to a relatively small increase in growth velocity observed in some, but not necessarily all, children in early to middle childhood. If present, the midchildhood growth spurt typically occurs sometime between the ages of 4 and 8 years, well before the onset of the far more pronounced pubertal growth spurt. In this study we used a triple logistic curve-fitting method to fit individual growth curves to serial stature data from 579 healthy participants in the Fels Longitudinal Study, 479 of whom have been genotyped for about 400 short tandem repeat (STR) markers spanning the genome. We categorized individuals according to the presence or absence of a midchildhood growth spurt and then conducted heritability and genome-wide linkage analyses on the dichotomous trait. In the total sample of 579 individuals, 336 (58%) were found to have evidence of having had a midchildhood growth spurt. There was a marked sex difference in presence of the midchildhood growth spurt, however, with 232 of the 293 males (79%) having had a midchildhood growth spurt but just 104 of the 286 females (36%) having had one. Presence of a midchildhood growth spurt was found to have a significant heritability of 0.37 ± 0.14 (p = 0.003). Two quantitative trait loci with suggestive LOD scores were found: one at 12 cM on chromosome 17p13.2 (LOD = 2.13) between markers D17S831 and D17S938 and one at 85 cM on chromosome 12q14 (LOD = 2.06) between markers D12S83 and D12S326.

Quantitative physical activity assessment of children and adolescents in a rural population from Eastern Nepal

We report cross‐sectional, objectively measured physical activity data for 399 children and adolescents aged 6 to 18 years. We evaluated physical activity of children and adolescents, considered time spent in each activity intensity category, and explored the impact of growth disruption (stunting and wasting) on physical activity patterns.