Genetics Analysis Workshop 16 Problem 2: tTe Framingham Heart Study Data

Genetic Analysis Workshop 16 (GAW16) Problem 2 presented data from the Framingham Heart Study (FHS), an observational, prospective study of risk factors for cardiovascular disease begun in 1948. Data have been collected in three generations of family participants in the study and the data presented for GAW16 included phenotype data from all three generations, with four examinations of data collected repeatedly for the first two generations. The trait data consisted of information on blood pressure, hypertension treatment, lipid levels, diabetes and blood glucose, smoking, alcohol consumed, weight, and coronary heart disease incidence. Additionally, genotype data obtained through a genome-wide scan (FHS SHARe) of 550,000 single-nucleotide polymorphisms from Affymetrix chips were included with the GAW16 data. The genotype data were also used for GAW16 Problem 3, where simulated phenotypes were generated using the actual FHS genotypes. These data served to provide investigators with a rich resource to study the behavior of genome-wide scans with longitudinally collected family data and to develop and apply new procedures.National Heart, Lung and Blood Institute (2 N01-HC-25195-06); National Institutes of Health (National Institute of General Medical Sciences R01 GM031575

Genome-Wide Association to Body Mass Index and Waist Circumference: The Framingham Heart Study 100K Project

BACKGROUND: Obesity is related to multiple cardiovascular disease (CVD) risk factors as well as CVD and has a strong familial component. We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study. METHODS: A total of 1341 Framingham Heart Study participants in 310 families genotyped with the Affymetrix 100K SNP GeneChip had adiposity traits measured over 30 years of follow up. Body mass index (BMI), waist circumference (WC), weight change, height, and radiographic measures of adiposity (subcutaneous adipose tissue, visceral adipose tissue, waist circumference, sagittal height) were measured at multiple examination cycles. Multivariable-adjusted residuals, adjusting for age, age-squared, sex, smoking, and menopausal status, were evaluated in association with the genotype data using additive Generalized Estimating Equations (GEE) and Family Based Association Test (FBAT) models. We prioritized mean BMI over offspring examinations (1–7) and cohort examinations (10, 16, 18, 20, 22, 24, 26) and mean WC over offspring examinations (4–7) for presentation. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg equilibrium p ≥ 0.001, and call rates of at least 80%. RESULTS: The top SNPs to be associated with mean BMI and mean WC by GEE were rs110683 (p-value 1.22*10-7) and rs4471028 (p-values 1.96*10-7). Please see for the complete set of results. We were able to validate SNPs in known genes that have been related to BMI or other adiposity traits, including the ESR1 Xba1 SNP, PPARG, and ADIPOQ. CONCLUSION: Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); Atwood (R01 DK066241); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1

On viscous propulsion in active transversely isotropic media

We report a corrigendum to the paper 'Viscous propulsion in active transversely-isotropic media' [J. Fluid Mech. 812, 501-524, 2017 / arxiv 1608.01451].Comment: 12 pages, 3 figure

Consistency of linkage results across exams and methods in the Framingham Heart Study

BACKGROUND: The repeated measures in the Framingham Heart Study in the Genetic Analysis Workshop 13 data set allow us to test for consistency of linkage results within a study across time. We compared regression-based linkage to variance components linkage across time for six quantitative traits in the real data. RESULTS: The variance components approach found 11 significant linkages, the regression-based approach found 4. There was only one region that overlapped. Consistency between exams generally decreased as the time interval between exams increased. The regression-based approach showed higher consistency in linkage results across exams. CONCLUSION: The low consistency between exams and between methods may help explain the lack of replication between studies in this field

Sex and age specific effects of chromosomal regions linked to body mass index in the Framingham Study

BACKGROUND: Previously, we reported significant linkage of body mass index (BMI) to chromosomes 6 and 11 across six examinations, covering 28 years, of the Framingham Heart Study. These results were on all individuals available at each exam, thus the sample size varied from exam to exam. To remove any effect of sample size variation we have now constructed six subsets; for each exam individuals were only included if they were measured at every exam, i.e. for each exam, included individuals comprise the intersection of the original six exams. This strategy preferentially removed older individuals who died before reaching the sixth exam, thus the intersection datasets are smaller (n = 1114) and significantly younger than the full datasets. We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets. RESULTS: Results from the sex-specific genome scans revealed 11 regions in which a sex-specific maximum lodscore was at least 2.0 for at least one dataset. Randomization tests indicated that all 11 regions had significant (p < 0.05) differences in sex-specific maximum lodscores for at least three datasets. The strongest sex-specific linkage was for men on chromosome 16 with maximum lodscores 2.70, 3.00, 3.42, 3.61, 2.56 and 1.93 for datasets 1–6 respectively. Results from the full genome scans revealed that linked regions on chromosomes 6 and 11 remained significantly and consistently linked in the intersection datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1 increased from 0.97 in the older original dataset to 4.23 in the younger smaller intersection dataset. This difference in maximum lodscores was highly significant (p < 0.0001), implying that the effect of this chromosome may vary with age. Age effects may also exist for the linked regions on chromosomes 6 and 11. CONCLUSION: Sex specific effects of chromosomal regions on BMI are common in the Framingham study. Some evidence also exists for age-specific effects of chromosomal regions

Use of high throughput sequencing to observe genome dynamics at a single cell level

With the development of high throughput sequencing technology, it becomes possible to directly analyze mutation distribution in a genome-wide fashion, dissociating mutation rate measurements from the traditional underlying assumptions. Here, we sequenced several genomes of Escherichia coli from colonies obtained after chemical mutagenesis and observed a strikingly nonrandom distribution of the induced mutations. These include long stretches of exclusively G to A or C to T transitions along the genome and orders of magnitude intra- and inter-genomic differences in mutation density. Whereas most of these observations can be explained by the known features of enzymatic processes, the others could reflect stochasticity in the molecular processes at the single-cell level. Our results demonstrate how analysis of the molecular records left in the genomes of the descendants of an individual mutagenized cell allows for genome-scale observations of fixation and segregation of mutations, as well as recombination events, in the single genome of their progenitor.Comment: 22 pages, 9 figures (including 5 supplementary), one tabl

Impact of Abamectin on Anagrus Nilaparvatae, an Egg Parasitoid of Nilaparvata Lugens

Anagrus nilaparvatae (Hymenoptera: Mymaridae) is an egg parasitoid potential for controlling the major pests on rice, the brown planthopper (Nilaparvata lugens [Hemiptera: Delphacidae]).Abamectin is one of insecticides registered for N. lugens. The research was aimed to investigate the impact of contact application of abamectin on the parasitism level of A. nilaparvatae under laboratory conditions. Adults of A. nilaparvatae and the first instars as well as adults of N. lugens were exposed to the residue of abamection inside the test tube. A. nilaparvatae was much more susceptible to abamectin compared to N. lugens. Application of abamectin at the recommended concentration (22.78 ppm) for 30 min caused 100% mortality, and it reduced to 85% when the concentration was decreased to 0.36 ppm. In contrast, the mortality for the first instar of N. lugens was only 15% at 22.78 and no mortality at 0.36 ppm. No N. lugens adults died even when they were exposed to 22.78 ppm. Furthermore, the parasitism test was conducted using 38 days after planting of IR-64 rice variety. Those plants were infested with 50 females of N. lugens for 2 days. A. nilaparvatae were exposed by contact to 0.02, 0.23, and 2.28 ppm of abamectin. The survivors were released to the rice plant containing eggs of N. lugens. Contact application of abamectin reduced parasitism level of A. nilaparvatae as much as 86.34, 70.01, and 28.43% with concentrations of 2.28 ppm, 0.23 and 0.02 ppm, respectively. In addition, the number of parasitoids emerged decreased with increasing concentration of abamectin. These results suggest that abamectin could be detrimental to A. nilaparvatae due to direct mortality, reduced the parasitism level, and decreased the number of progeny produced. IntisariAnagrus nilaparvatae (Hymenoptera: Mymaridae) merupakan salah satu parasitoid telur yang berpotensi untuk mengendalikan hama utama tanaman padi, wereng batang padi cokelat (Nilaparvata lugens [Hemiptera: Delphacidae]). Abamektin adalah salah satu insektisida yang terdaftar untuk pengendalian N. lugens. Penelitian ini bertujuan untuk mengetahui dampak aplikasi kontak abamektin terhadap suseptibilitas dan tingkat parasitasi A. nilaparvatae terhadap telur N. lugens pada kondisi laboratorium. Imago A. nilaparvatae serta instar satu dan imago N. lugens dipapar dengan residu abamektin di dalam tabung reaksi. A. nilaparvatae lebih peka terhadap abamektin dibandingkan N. lugens. Aplikasi abamektin pada konsentrasi anjuran (22,78 ppm) selama 30 menit menyebabkan mortalitas A. nilaparvatae 100%, dan mengurangi sampai dengan 85% pada konsentrasi yang lebih rendah 0,36 ppm. Sebaliknya, mortalitas instar satu N. lugens hanya sebesar 15% pada 22,78 ppm dan tidak menimbulkan kematian pada 0,36 ppm. Konsentrasi 22,78 ppm tidak menimbulkan kematian imago N. lugens. Selanjutnya, uji parasitasi dilakukan menggunakan media tanaman padi varietas IR-64 umur 38 hari setelah tanam. Tanaman diinfestasi dengan 50 ekor betina N. lugens selama dua hari. A. nilaparvatae dipapar abamektin dengan metode kontak pada konsentrasi 0.02, 0,23, dan 2,28 ppm. Parasitoid yang mampu bertahan hidup dilepaskan pada tanaman padi yang telah diinfestasi telur N. lugens. Aplikasi kontak abamektin mengurangi tingkat parasitasi A. nilaparvatae sebesar 86,34, 70.01, dan 28,43% pada konsentrasi 2,28; 0,23; dan 0,02 ppm. Selain itu, jumlah parasitoid yang muncul semakin menurun dengan peningkatan konsentrasi abamektin. Hasil ini menunjukkan bahwa abamektin dapat merugikan secara langsung terhadap mortalitas serta mengurangi tingkat parasitasi dan jumlah keturunan A. nilaparvatae

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)(1). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%