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 < 5.0 × 10−8) near FTO (P = 3.72 × 10−23), TMEM18 (P = 3.24 × 10−17), MC4R (P = 4.41 × 10−17), TNNI3K (P = 4.32 × 10−11), SEC16B (P = 6.24 × 10−9), GNPDA2 (P = 1.11 × 10−8) and POMC (P = 4.94 × 10−8) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10−5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different age

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countrie

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. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

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 x 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. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.Peer reviewe

Brief Communications:Effect of Storage Time and Temperature on DNA Extracted from Whole Blood Samples

The development of recombinant DNA technology has made it possible to examine heritable variation directly at the DNA sequence level. However, incorporating these techniques and methods in anthropologic field studies still presents several logistic problems and concerns, starting with the possible negative effects of storage and transport on the requisite blood samples. In this regard, though, the successful extraction and analysis of DNA from tissues thousands of years old is encouraging and suggests that such problems may be overcome (Paabo 1985; Paabo et al. 1988). Nonetheless, more data on the quality and quantity of DNA extracted from whole blood samples obtained from living individuals and handled under field conditions are needed. Here we report the findings of an initial experiment designed to simulate best, worst, and indifferent treatment of blood samples. High-molecular-weight genomic DNA was extracted from the samples following storage, its quantity measured, and its quality assessed by electrophoresis and hybridization of restriction fragments

Generational Change in Skin Color Variation among Habbani Yemeni Jews

The Habbani Yemeni Jews were a religious isolate in Yemen for centuries. Since a bottleneck in the late eighteenth century the population, composed of six patrilineages, has steadily grown. Isonymy analysis of Habbani genealogies reveals a significant increase in lineage endogamy by the early twentieth century, suggesting that microdifferentiation of Habbani population genetic structure along the patrilineages was occurring. We examine reflectance data from a “parental” generation of 159 individuals studied by Hulse in the 1960s and reflectance data from an “offspring” generation of 243 individuals studied by Towne in the 1980s. A greater amount of interlineage skin color differences is found in the offspring generation than in the parental generation. This finding is consistent with what is known of the evolution of Habbani population genetic structure

The Belated Autopsy and Identification of an Eighteenth Century Naval Hero—The Saga of John Paul Jones

John Paul Jones, the “Father of the American Navy,” is known for the battletime assertion that he had “not yet begun to fight.” His central role in a triumph of scientific forensic identification more than a century after his death is less known. John Paul Jones died in 1792 and was buried in Paris, France. The location of his grave was lost over time and a search for his corpse began in 1899. Remains matching his physical characteristics and circumstance of burial were discovered in 1905 and returned to the United States for a hero\u27s burial. Some questioned the identification at the time and the major source of identifying information (17) has since been shown to contain false information. The published forensic literature fails to address existing critiques of the identification. We provide a substantive analysis and conclude that the available evidence supports the identification of the unknown remains as those of John Paul Jones

The Belated Autopsy and Identification of an Eighteenth Century Naval Hero—The Saga of John Paul Jones

John Paul Jones, the “Father of the American Navy,” is known for the battletime assertion that he had “not yet begun to fight.” His central role in a triumph of scientific forensic identification more than a century after his death is less known. John Paul Jones died in 1792 and was buried in Paris, France. The location of his grave was lost over time and a search for his corpse began in 1899. Remains matching his physical characteristics and circumstance of burial were discovered in 1905 and returned to the United States for a hero\u27s burial. Some questioned the identification at the time and the major source of identifying information (17) has since been shown to contain false information. The published forensic literature fails to address existing critiques of the identification. We provide a substantive analysis and conclude that the available evidence supports the identification of the unknown remains as those of John Paul Jones

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

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

Genetic Analysis of Patterns of Growth in Infant Recumbent Length

A genetic basis to growth and development has been demonstrated in many heritability studies of anthropometries. Although such measures describe the extent of grow that particular times, they do not fully address the process of growth. We applied a three-parameter curve-fitting function to serial measures of recumbent length from 569 infants (birth to 2 years of age) in 188 families enrolled in the Fels Longitudinal Study. This yielded three growth pattern parameters that represented estimated recumbent length at birth (parameter 1), rate of growth (parameter 2), and intrinsic rate of change in growth (parameter 3). The growth pattern parameter estimates for each individual were examined in a series of genetic analyses using a maximum -likelihood method for pedigree data. Significant heritabilities were found for all three growth pattern parameters: parameter 1, h2 — 0.83 ± 0.12; parameter 2, h2 = 0.67 ± 0.18; and parameter 3, h2 = 0.78 ± 0.17. In addition, genotype by sex interaction was indicated for growth pattern parameters 2 and 3, suggesting that the genes influencing rate of growth and intrinsic rate of change in growth are them selves influenced by the sex of the individual