Food insecurity and obesity: research gaps, opportunities, and challenges.

Food insecurity, defined as a lack of consistent access to enough food for an active, healthy life, is a major public health concern with 11.8% of U.S. households (15.0 million) estimated to be affected at some point in 2017 according to the United States Department of Agriculture Economic Research Service. While the link between food insecurity, diet quality, and obesity is well documented in the literature, additional research and policy considerations are needed to better understand underlying mechanisms, associated risks, and effective strategies to mitigate the adverse impact of obesity related food insecurity on health. With its Strategic Plan for NIH Obesity Research, the NIH has invested in a broad spectrum of obesity research over the past 10 years to understand the multifaceted factors that contribute to the disease. The issue of food insecurity, obesity and nutrition is cross-cutting and relates to many activities and research priorities of the institutes and centers within the NIH. Several research gaps exist, including the mechanisms and pathways that underscore the complex relationship between food insecurity, diet, and weight outcomes, the impacts on pregnant and lactating women, children, and other vulnerable populations, its cumulative impact over the life course, and the development of effective multi-level intervention strategies to address this critical social determinant of health. Challenges and barriers such as the episodic nature of food insecurity and the inconsistencies of how food insecurity is measured in different studies also remain. Overall, food insecurity research aligns with the upcoming release of the Strategic Plan for NIH Nutrition Research and will continue to be prioritized in order to enhance health, lengthen life, reduce illness and disability and health disparities.

Challenges and solutions for gene identification in the presence of familial locus heterogeneity.

Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra- and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification.

Decision making in eating behavior: state of the science and recommendations for future research.

BACKGROUND: The National Institutes of Health Division of Nutrition Research Coordination, the National Cancer Institute, the National Health Lung and Blood Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Diabetes, Digestive and Kidney Diseases convened a scientific workshop entitled "Decision Making in Eating Behavior: Integrating Perspectives from the Individual, Family, and Environment" in April 2008 PURPOSE/METHODS: The purpose of this paper is to provide a synthesis of the workshop. RESULTS: The common themes that ran throughout the conference were as follows: (1) Initiating behavior differs conceptually from sustaining behaviors; (2) The intersection of biology, genetics, and environment (physical, political, economic, and social) is where eating behavior occurs; (3) Marketing and advertising influence eating behavior influence; and (4) sometimes, seemingly unrelated policies influence eating behavior. CONCLUSIONS: Additional research is needed.

The change in weight perception of weight status among the overweight: comparison of NHANES III (1988-1994) and 1999-2004 NHANES.

OBJECTIVES: This study seeks to determine whether perception of weight status among the overweight has changed with the increasing overweight/obesity prevalence. METHODS: The perception of weight status was compared between overweight participants (BMI between 25.0-29.9 kg/m2) from NHANES III (1988-1994) and overweight participants from NHANES 1999-2004. Perception of weight status was assessed by asking participants to classify their weight as about the right weight, underweight or overweight. Comparisons were made across age groups, genders, race/ethnicities and various income levels. RESULTS: Fewer overweight people during the NHANES 1999-2004 survey perceived themselves as overweight when compared to overweight people during the NHANES III survey. The change in distortion between the survey periods was greatest among persons with lower income, males and African-Americans. CONCLUSION: The increase in overweight/obesity between the survey years (NHANES III and NHANES 1999-2004 has been accompanied with fewer overweight people perceiving themselves as overweight.

Expression of GJB2 and GJB6 is reduced in a novel DFNB1 allele.

In a large kindred of German descent, we found a novel allele that segregates with deafness when present in trans with the 35delG allele of GJB2. Qualitative polymerase chain reaction-based allele-specific expression assays showed that expression of both GJB2 and GJB6 from the novel allele is dramatically reduced. This is the first evidence of a deafness-associated regulatory mutation of GJB2 and of potential coregulation of GJB2 and GJB6.

Connexin 26 35delG does not represent a mutational hotspot.

Non-syndromic hearing impairment (NSHI) is the most common form of deafness and presents with no other symptoms or sensory defects. Mutations in the gap junction gene GJB2 account for a high proportion of recessive NSHI. The GJB2 gene encodes connexin 26, which forms plasma membrane channels between cochlear cells. In Caucasian populations a single mutation, 35delG, accounts for most cases of NSHI. This mutation appears to be most prevalent in individuals of Mediterranean European descent, with carrier frequencies estimated as being as high as one in thirty. The 35delG region may be a mutational hotspot. The mutation arises from the deletion of a guanine from a six-guanine stretch and nearby microsatellite markers show little evidence for linkage disequilibrium. We believe that 35delG is an old mutation in a chromosomal region of high recombination. The genetic context of the 35delG mutation was examined to distinguish between an old or a recurring mutation. We identified two single-nucleotide polymorphisms (SNPs) immediately upstream of the first exon of GJB2. Polymerase chain reaction/restriction fragment length polymorphism analysis determined the SNP genotype of 35delG containing chromosomes from various populations, including Italy, Brazil, and North America. We found the same, relatively rare, polymorphism associated with the 35delG mutation in all populations studied. We have also examined microsatellite markers D13S175, which is 80 kb telomeric to GJB2, and D13S1316, which is 80 kb centromeric to GJB2. D13S175 appears to be in weak linkage disequilibrium with 35delG, while D13S1316 is less so. SNPs located between the 35delG mutation and the microsatellite markers show strong evidence of linkage disequilibrium. Taken together, these results indicate there has been substantial recombination near the 35delG mutation; however, we present evidence that the 35delG mutation arose in European and Middle Eastern populations from a single mutational event on a founder chromosome.