| 11. |
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| 12. |
- Kathiresan, Sekar, et al.
(author)
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A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study
- 2007
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In: BMC Medical Genetics. - 1471-2350. ; 8
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Journal article (peer-reviewed)abstract
- Background: Blood lipid levels including low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol ( HDL-C), and triglycerides ( TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes. Methods: In 1087 Framingham Heart Study Offspring cohort participants ( mean age 47 years, 52% women), we conducted genome-wide analyses ( Affymetrix 100K GeneChip) for fasting blood lipid traits. Total cholesterol, HDL-C, and TG were measured by standard enzymatic methods and LDL-C was calculated using the Friedewald formula. The long-term averages of up to seven measurements of LDL-C, HDL-C, and TG over a similar to 30 year span were the primary phenotypes. We used generalized estimating equations ( GEE), family-based association tests ( FBAT) and variance components linkage to investigate the relationships between SNPs ( on autosomes, with minor allele frequency >= 10%, genotypic call rate >= 80%, and Hardy-Weinberg equilibrium p >= 0.001) and multivariable-adjusted residuals. We pursued a three-stage replication strategy of the GEE association results with 287 SNPs ( P < 0.001 in Stage I) tested in Stage II ( n similar to 1450 individuals) and 40 SNPs ( P < 0.001 in joint analysis of Stages I and II) tested in Stage III ( n similar to 6650 individuals). Results: Long-term averages of LDL-C, HDL-C, and TG were highly heritable ( h(2) = 0.66, 0.69, 0.58, respectively; each P < 0.0001). Of 70,987 tests for each of the phenotypes, two SNPs had p < 10(-5) in GEE results for LDL-C, four for HDL-C, and one for TG. For each multivariable-adjusted phenotype, the number of SNPs with association p < 10(-4) ranged from 13 to 18 and with p < 10(-3), from 94 to 149. Some results confirmed previously reported associations with candidate genes including variation in the lipoprotein lipase gene ( LPL) and HDL-C and TG ( rs7007797; P = 0.0005 for HDL-C and 0.002 for TG). The full set of GEE, FBAT and linkage results are posted at the database of Genotype and Phenotype (dbGaP). After three stages of replication, there was no convincing statistical evidence for association ( i.e., combined P < 10(-5) across all three stages) between any of the tested SNPs and lipid phenotypes. Conclusion: Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects ( i.e., < 1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
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| 13. |
- Lapidus, L, et al.
(author)
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Alcohol intake among women and its relationship to diabetes incidence and all-cause mortality: the 32-year follow-up of a population study of women in Gothenburg, Sweden
- 2005
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In: Diabetes Care. ; 28, s. 2230-2235
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Journal article (peer-reviewed)abstract
- Department of Primary Health Care, Sahlgrenska Uni, Göteborg University, Box 454 S-405 30 Göteborg, Sweden. leif.lapidus@swipnet.se OBJECTIVE: The purpose of the study was to explore the predictive value of women's alcohol habits in relation to incidence of diabetes and all-cause mortality. Special attention was paid to potential confounding factors such as age, heredity, education, socioeconomic group, physical inactivity, smoking, blood pressure, serum lipids, and, in particular, obesity. RESEARCH DESIGN AND METHODS: A longitudinal population study consisting of a representative sample of 1,462 women aged 38-60 started in Göteborg, Sweden, in 1968-1969 monitoring for diabetes and mortality over 32 years. RESULTS: Alcohol intake, expressed as intake of wine, hard liquor, or total grams of alcohol, was significantly negatively associated to 32-year diabetes incidence independent of age. However, the apparently protective effect of the alcohol variables was attenuated when BMI was included as a covariate. The inverse relationship between wine intake and diabetes did not remain after adjustment for physical activity or socioeconomic group. Beer and wine intake were significantly negatively associated to mortality. Increase of alcohol intake between the examination in 1968-1969 and 1980-1981 was significantly inversely related to the mortality between 1980-1981 and 2000-2001 and independent of all covariates. No relationship was observed between an increase in alcohol intake and diabetes incidence. However, after adjustment for age, family history, and basal alcohol consumption altogether, a significant inverse relationship was observed between increase of alcohol and diabetes incidence. CONCLUSIONS: The initially significant inverse associations observed between alcohol and diabetes as well as mortality were dependent on a number of confounding factors, of which BMI seems to be the most important. PMID: 16123495 [PubMed - indexed for MEDLINE]
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| 14. |
- Lissner, Lauren, 1956, et al.
(author)
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OPEN about obesity: recovery biomarkers, dietary reporting errors and BMI
- 2007
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In: International Journal of Obesity. ; 31, s. 956-961
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Journal article (peer-reviewed)abstract
- Department of Public Health and Community Medicine, Sahlgrenska Academy at Göteborg University, Sweden, and Research Unit for Dietary Studies at Institute of Preventive Medicine, Copenhagen University Hospital, Denmark. Lauren.lissner@medfak.gu.se OBJECTIVE: Obesity-related under-reporting of usual dietary intake is one of the most persistent sources of bias in nutrition research. The aim of this paper is to characterize obese and non-obese individuals with respect to reporting errors observed with two common dietary instruments, using energy and protein recovery biomarkers as reference measures. POPULATION AND METHODS: This report employs data from the Observing Protein and Energy Nutrition (OPEN) study. Analyses are based on stratified samples of 211 (57 obese) men and 179 (50 obese) women who completed 24-h recalls (24HR), food frequency questionnaires (FFQ), doubly labelled water (DLW) and urinary nitrogen (UN) assessments. RESULTS: In obese and non-obese subgroups, FFQ yielded lower energy and protein intake estimates than 24HR, although biomarker-based information indicated under-reporting with both dietary instruments. Gender differences in obesity-related bias were noted. Among women, the DLW-based energy requirement was 378 kcal greater in obese than in non-obese groups; the FFQ was able to detect a statistically significant portion of this extra energy, while the 24HR was not. Among men, the DLW-based energy requirement was 485 kcal greater in the obese group; however, neither FFQ nor 24HR detected this difference in energy requirement. Combining protein and energy estimates, obese men significantly over-reported the proportion of energy from protein using the 24HR, but not with the FFQ. In obese women, no significant reporting error for energy percent protein was observed by either method. At the individual level, correlations between energy expenditure and reported energy intake tended to be weaker in obese than non-obese groups, particularly with the 24HR. Correlations between true and reported protein density were consistently higher than for protein or energy alone, and did not vary significantly with obesity. CONCLUSION: This work adds to existing evidence that neither of these commonly used dietary reporting methods adequately measures energy or protein intake in obese groups. The 24HR, while capturing more realistic energy distributions for usual intake, may be particularly problematic in the obese. PMID: 17299385 [PubMed - indexed for MEDLINE]
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| 15. |
- Murphy, Lauren L., et al.
(author)
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An Hedonomic Evaluation of the Effect of Repeated System-Exposure on Pleasurable Human-System Experience
- 2008
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In: Proceedings of the Human Factors and Ergonomics Society Annual Meeting September 2008 vol. 52 no. 6. - Santa Monica, CA, USA : Human Factors and Ergonomics Society. - 2169-5067. - 9781605606859 ; , s. 518-522
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Conference paper (peer-reviewed)abstract
- We report on two studies of the mere exposure effect on the occurrence of flow. Findings reveal that: (a) pleasurable human-system experience increased linearly with repeated exposure to the technology of interest; (b) an habituation effect of flow was mediated by day; (c) performance was positively correlated to flow. Suggestions for future research directions for Hedonomics include mitigating the habituation of flow effect by incorporating an adaptive hedonomic design to reduce the effect of boredom that comes with familiar stimuli an approach that enables the user to create a balance between typicality and novelty in order to allow for changing cultural norms and personal change over time.
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| 16. |
- Shionoya, Kiseko, 1964-, et al.
(author)
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Development switch in neural circuitry underlying odor-malaise learning
- 2006
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In: Learning & memory (Cold Spring Harbor, N.Y.). - : Cold Spring Harbor Laboratory Press (CSHL). - 1072-0502 .- 1549-5485. ; 13:6, s. 801-808
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Journal article (peer-reviewed)abstract
- Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.
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| 17. |
- Tao, Yi, et al.
(author)
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Rapid synthesis of auxin via a new tryptophan-dependent pathway is required for shade avoidance in plants
- 2008
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In: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 133:1, s. 164-176
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Journal article (peer-reviewed)abstract
- Plants grown at high densities perceive a decrease in the red to far-red (R:FR) ratio of incoming light, resulting from absorption of red light by canopy leaves and reflection of far-red light from neighboring plants. These changes in light quality trigger a series of responses known collectively as the shade avoidance syndrome. During shade avoidance, stems elongate at the expense of leaf and storage organ expansion, branching is inhibited, and flowering is accelerated. We identified several loci in Arabidopsis, mutations in which lead to plants defective in multiple shade avoidance responses. Here we describe TAA1, an aminotransferase, and show that TAA1 catalyzes the formation of indole-3-pyruvic acid (IPA) from L-tryptophan (L-Trp), the first step in a previously proposed, but uncharacterized, auxin biosynthetic pathway. This pathway is rapidly deployed to synthesize auxin at the high levels required to initiate the multiple changes in body plan associated with shade avoidance.
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