The Prevalence of Glaucoma in the Jirel Ethnic Group of Nepal.

Glaucoma is one of the leading causes of blindness worldwide with individuals in Asia disproportionately affected. Using a cross-sectional study design as part of the Jiri Eye Study, we assessed the prevalence of glaucoma in the Jirel population of Nepal and provide new information on the occurrence of glaucoma in south central Asia. Over a four-year period, 2,042 members of the Jirel population, aged 18 years and older, underwent a detailed ocular examination.

Glycated Serum Protein Genetics and Pleiotropy with Cardiometabolic Risk Factors.

Measurements of fasting glucose (FG) or glycated hemoglobin A1c (HbA1c) are two clinically approved approaches commonly used to determine glycemia, both of which are influenced by genetic factors. Obtaining accurate measurements of FG or HbA1c is not without its challenges, though. Measuring glycated serum protein (GSP) offers an alternative approach for assessing glycemia.

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass.

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

Objectives: 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.

Methods: Participants wore an Actical (Mini-Mitter, Bend, OR) omnidirectional accelerometer for one week as part of their annual visit to the Jiri Growth Study.

The positive association of obesity variants with adulthood adiposity strengthens over an 80-year period: a gene-by-birth year interaction.

Objective: To test the hypothesis that the statistical effect of obesity-related genetic variants on adulthood adiposity traits depends on birth year.

Methods: The study sample included 907 related, non-Hispanic White participants in the Fels Longitudinal Study, born between 1901 and 1986, and aged 25-64.99 years (474 females; 433 males) at the time of measurement.

Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal.

Objectives: 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.

Methods: The Jirel ethnic group of eastern Nepal participates in various genetic epidemiologic studies, including those in which hand-wrist radiographs have been taken to examine skeletal development.

Systematic examination of infant size and growth metrics as risk factors for overweight in young adulthood.

Objective: To systematically examine infant size and growth, according to the 2006 WHO infant growth standards, as risk factors for overweight status in young adulthood in a historical cohort. Specifically, to assess: Whether accounting for length (weight-for-length) provides a different picture of risk than weight-for-age, intervals of rapid growth in both weight-for-age and weight-for-length metrics, and what particular target ages for infant size and intervals of rapid growth associate most strongly with overweight as a young adult.

Patients/methods: Data analysis of 422 appropriate for gestational age white singleton infants enrolled in the Fels Longitudinal Study.

Gene-by-age effects on BMI from birth to adulthood: the Fels Longitudinal Study.

Objectives: Genome wide association studies have shown 32 loci to influence BMI in European-American adults but replication in other studies is inconsistent and may be attributed to gene-by-age effects. The aims of this study were to determine if the influence of the summed risk score of these 32 loci (GRS) on BMI differed across age from birth to 40 years, and to determine if additive genetic effects other than those in the GRS differed by age.

Methods: Serial measures of BMI were calculated at 0, 1, 3, 6, 9, 12, 18, and 28 months, and 4, 7, 11, 15, 19, 23, 30, and 40 years for 1,176 (605 females, 571 males) European-American participants in the Fels Longitudinal Study.

Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.

Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.

Characterization of the infant BMI peak: sex differences, birth year cohort effects, association with concurrent adiposity, and heritability.

Objectives: To characterize an early trait in the BMI-for-age curve, the infant BMI peak.

Methods: BMI-for-age curves were produced for 747 non-Hispanic, white Fels Longitudinal Study participants, from which individual age (AgePeak ) and BMI (BMIPeak ) at maximum infant BMI were estimated. Multivariable general linear regression was used to examine the effects of sex and birth year cohort (1929-1950, 1951-1970, and 1971-2010) on AgePeak and BMIPeak , with associations between BMIPeak and concurrent sum of four skinfold thicknesses assessed in a subsample (N = 155).

Predicting the timing of maturational spurts in skeletal age.

Measures of maturity provide windows into the timing and tempo of childhood growth and maturation. Delayed maturation in a single child, or systemically in a population, can result from either genetic or environmental factors. In terms of the skeleton, delayed maturation may result in short stature or indicate another underlying issue.

Genetic risk for earlier menarche also influences peripubertal body mass index.

It is unclear whether earlier age at menarche is associated with higher body mass index (BMI) because they share a common genetic underpinning. We investigated the impact of single nucleotide polymorphisms (SNPs) influencing menarche timing on peripubertal BMI. For 556 Fels Longitudinal Study children (277 boys/279 girls) born 1928-1992, a genetic risk score (GRS(42)) was computed as the sum of the number of risk alleles in 42 putative menarche SNPs.

Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women.

Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n = 4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck.

Associations between trunk, leg and total body adiposity with arterial stiffness.

Background: Obesity and arterial stiffness are associated, but fat distribution patterns may be more strongly related to arterial stiffness than general obesity because of the possible increased inflammation associated with increased abdominal adiposity. The aims of this study were to examine whether fat patterning is associated with arterial stiffness, and determine whether these associations are mediated by low-grade inflammation.

Methods: Adult participants from the Fels Longitudinal Study (228 males and 254 females) were assessed for brachial-ankle pulse wave velocity (BaPWV) to determine arterial stiffness.

The influence of age at menarche on cross-sectional geometry of bone in young adulthood.

Elucidating the somatic and maturational influences on the biomechanical properties of bone in children is crucial for a proper understanding of bone strength and quality in childhood and later life, and has significant potential for predicting adult fracture and osteoporosis risks. The ability of a long bone to resist bending and torsion is primarily a function of its cross-sectional geometric properties, and is negatively impacted by smaller external bone diameter. In pubescent girls, elevated levels of estrogen impede subperiosteal bone growth and increase endosteal bone deposition, resulting in bones averaging a smaller external and internal diameter relative to boys.

A changing pattern of childhood BMI growth during the 20th century: 70 y of data from the Fels Longitudinal Study.

Background: The BMI distribution shifted upward in the United States between the 1960s and the 1990s, but little is known about secular trends in the pattern of BMI growth, particularly earlier in the century and early in childhood.

Objective: The objective was to examine differences in BMI growth in children born in 1929-1999.

Design: BMI curves from ages 2 to 18 y were produced for 855 European-American children in the Fels Longitudinal Study born in 1929-1953, 1954-1972, and 1973-1999.

Eighty-year trends in infant weight and length growth: the Fels Longitudinal Study.

Objectives: To investigate secular trends in weight and length growth from birth to 3 years of age in infants born from 1930 to 2008, and to assess whether these trends were associated with concurrent trends in pace of infant skeletal maturation and maternal body mass index.

Study Design: Longitudinal weight and length data from 620 infants (302 girls) were analyzed with mixed effects modeling to produce growth curves and predicted anthropometry for infants born from 1930 to 1949, 1950 to 1969, 1970 to 1989, and 1990 to 2008.

Results: The most pronounced differences in growth occurred in the first year of life.

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.

Cortical bone health shows significant linkage to chromosomes 2p, 3p, and 17q in 10-year-old children.

Genes play an important role in lifelong skeletal health. Genes that influence bone building during childhood have the potential to affect bone health not only throughout childhood but also into adulthood. Given that peak bone mass is a significant predictor of adult fracture risk, it is imperative that the genetic underpinnings of the normal pediatric skeleton are uncovered.

Sugar-sweetened and diet beverages in relation to visceral adipose tissue.

Frequent sugar-sweetened beverage (SSB) intake has been consistently associated with increased adiposity and cardio-metabolic risk, whereas the association with diet beverages is more mixed. We examined how these beverages associate with regional abdominal adiposity measures, specifically visceral adipose tissue (VAT). In a cross-sectional analysis of 791 non-Hispanic white men and women aged 18-70 we examined how beverage consumption habits obtained from a food frequency questionnaire associate with overall and abdominal adiposity measures from MRI.

Differences in the heritability of growth and growth velocity during infancy and associations with FTO variants.

While the associations of common variants in the FTO gene with obesity have been widely replicated in adults, there is conflicting evidence regarding their effects in infancy. We hypothesize that the genetic influences on growth traits vary during infancy, and that conflicting results may stem from variation in the ages at which FTO associations have been examined. Using longitudinal weight and length data at 0, 1, 3, 6, 9, 12, 18, 24, 30, and 36 months in 917 (444 females, 473 males) family members from the Fels Longitudinal Study, we used a variance components-based approach (SOLAR) to: (i) examine differences in heritability (gene-by-age interaction) in weight, length, relative weight (BMI and ponderal index (PI)) and instantaneous weight and length velocities over the course of infancy, and (ii) test whether a common FTO variant (rs9939609) was associated with infant growth at three ages (maximum trait heritability, birth and 36 months).

Secular trends in blood pressure during early-to-middle adulthood: the Fels Longitudinal Study.

Background: Some studies have shown a decline in blood pressure (BP) over the second half of the twentieth century. However, the increasing prevalence of obesity may have opposite effects on recent cohorts.

Method: Using serial BP data from the Fels Longitudinal Study, we examined secular trends in mean BP, the rate of change in BP with age (slopes), and the influence of obesity (i.

A genome-wide linkage scan for quantitative trait loci influencing the craniofacial complex in humans (Homo sapiens sapiens).

The genetic architecture of the craniofacial complex has been the subject of intense scrutiny because of the high frequency of congenital malformations. Numerous animal models have been used to document the early development of the craniofacial complex, but few studies have focused directly on the genetic underpinnings of normal variation in the human craniofacial complex. This study examines 80 quantitative traits derived from lateral cephalographs of 981 participants in the Fels Longitudinal Study, Wright State University, Dayton, Ohio.

Significant associations of age, menopausal status and lifestyle factors with visceral adiposity in African-American and European-American women.

Background: Elevated visceral adiposity is strongly predictive of cardiometabolic disease, but, due to the high cost of biomedical imaging, assessment of factors contributing to normal variation in visceral (VAT) and subcutaneous (SAT) adipose tissue partitioning in large cohorts of healthy individuals are few, particularly in ethnic and racial minority populations.

Objective: To describe age, menopausal status, smoking and physical activity differences in VAT and abdominal subcutaneous adipose tissue (ASAT) mass in African-American (AA) and European-American (EA) women.

Methods: Magnetic resonance imaging measures of VAT and ASAT mass and VAT% (VAT/VAT+ASAT, %) were obtained from a cross-sectional sample of 617 EA and 111 AA non-diabetic women aged 18-80 years.