Mobile phone use and location of glioma: A case–case analysis

We assessed a new approach for evaluating the glioma risk among users of mobile phones to focus on the part of the brain most heavily exposed to radiofrequency electromagnetic fields from mobile phones. The tumor midpoint was defined from radiological imaging. A case–case analysis with 99 gliomas was performed using logistic regression. The exposed cases were those with the tumor mid‐point within 4.6 cm from the line between the mouth and the external meatus of the ear, representing the most likely location of the mobile phone (the source of exposure). Alternative analyses based on various indicators of mobile phone use as the outcome were also carried out. The majority of cases were regular mobile phone users. A slightly higher proportion of gliomas among mobile phone users than non‐users occurred within 4.6 cm from the presumed location of the mobile phone (28% vs. 14%). Modestly elevated odds ratios were observed for several indicators of mobile phone use, but without an exposure gradient. The highest odds ratios were found for contralateral and short‐term use. Our results, though limited by the small sample size, demonstrate that detailed information on tumor location allows evaluation of the risk related to the most heavily exposed part of the brain, representing direct evaluation of the possible local carcinogenic effects of the radiofrequency fields. However, field strength varies between users and over time also within a given anatomic site, due to the output power of the phone. Collaborative analysis of a larger sample is planned. Bioelectromagnetics 30:176–182, 2009. © 2009 Wiley‐Liss, Inc.     

Contribution of regulatory and structural variations in APOE to predicting dyslipidemia

The objective of this study was to evaluate 1) whether non single nucleotide polymorphisms-coding (non-cSNP) in the apolipoprotein E gene (APOE) identified by resequencing studies contribute to statistically explaining dyslipidemia if variations in the two cSNPs in exon 4 that define the 2, 3, and 4 alleles are ignored, and 2) whether the contribution of these additional SNPs persists when variations in the cSNPs are considered. We used an ecological, multiple-population, data-mining strategy to identify single-SNP and two-SNP genotypes that distinguish between high and low levels of plasma lipids in three training samples, European-Americans from Rochester, MN, African-Americans from Jackson, MS, and Europeans from North Karelia, Finland. We found that a pair of SNPs located in the 5' region define genotypes A560T832/A560T832, A560T832/A560G832, and A560T832/T560T832, which distinguish between high and low levels of HDL-cholesterol (HDL-C), triglycerides (TG), and/or total cholesterol (T-C). The A560T832/- genotypes predicted high TG and high T-C in both genders in a large independent test sample from Copenhagen, Denmark. Prediction of high T-C in the Danish females was dependent on genotypes defined by the cSNPs. Our study suggests that both regulatory and structural variations should be considered when evaluating the utility of APOE for predicting dyslipidemia in the population at large.     

Common variants show predicted polygenic effects on height in the tails of the distribution, except in extremely short individuals

Common genetic variants have been shown to explain a fraction of the inherited variation for many common diseases and quantitative traits, including height, a classic polygenic trait. The extent to which common variation determines the phenotype of highly heritable traits such as height is uncertain, as is the extent to which common variation is relevant to individuals with more extreme phenotypes. To address these questions, we studied 1,214 individuals from the top and bottom extremes of the height distribution (tallest and shortest ∼1.5%), drawn from ∼78,000 individuals from the HUNT and FINRISK cohorts. We found that common variants still influence height at the extremes of the distribution: common variants (49/141) were nominally associated with height in the expected direction more often than is expected by chance (p<5×10⁻²⁸), and the odds ratios in the extreme samples were consistent with the effects estimated previously in population-based data. To examine more closely whether the common variants have the expected effects, we calculated a weighted allele score (WAS), which is a weighted prediction of height for each individual based on the previously estimated effect sizes of the common variants in the overall population. The average WAS is consistent with expectation in the tall individuals, but was not as extreme as expected in the shortest individuals (p<0.006), indicating that some of the short stature is explained by factors other than common genetic variation. The discrepancy was more pronounced (p<10⁻⁶) in the most extreme individuals (height<0.25 percentile). The results at the extreme short tails are consistent with a large number of models incorporating either rare genetic non-additive or rare non-genetic factors that decrease height. We conclude that common genetic variants are associated with height at the extremes as well as across the population, but that additional factors become more prominent at the shorter extreme.     

Hypothesis-Based Analysis of Gene-Gene Interactions and Risk of Myocardial Infarction

The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3-2.0, depending on allele frequency and interaction model).     

Electron microscopic map of divisions 61, 62, and 63 of the salivary gland 3L chromosome in Drosophila melanogaster

The banding pattern in the three distal divisions of the salivary gland 3L chromosome of Drosophila melanogaster was analysed with electron microscopy (EM). New maps for divisions 61, 62, and 63 were drawn on the basis of electron micrographs taken from thin-sectioned squash preparations. Observations showed 41 regularly and 16 occasionally detectable new bands in these three divisions. On the other hand, only 9 of 24 Bridges' doublets also appeared as double bands on the EM maps. Accordingly, the total number of bands is more than 25% higher in the EM maps of divisions 61–63 than in Bridges' revised map of 3L. At least 13 sites of puffing activity can be localized in the electron micrographs of divisions 61–63.Dedicated to Prof. Dr. Hans Bauer on the occasion of his 80th birthday on September 27, 1984     

Cardiorespiratory and subjective responses to prolonged arm and leg exercise in healthy young and older men

Ten young (aged 23–30 years) and nine older (aged 54–59 years) healthy men with a similar size of limb muscle mass performed arm crank and leg cycle exercise for 30 min at relative exercise intensities of 50% and 75% of maximal oxygen uptake for the corresponding muscle group. In the tests, heart rate, blood pressure, gas exchange variables, rating of perceived exertion and blood lactate concentration were measured. The limb muscle mass was determined by anthropometric measurements. At the 75% target exercise level, four of the older men and two of the young men could not complete the arm-cranking test, and one of the older men and two of the young men could not complete the leg-cycle test. During arm-cranking the absolute exercise intensity was similar for the young and older men because of similar maximal values during arm-cranking. But during leg-cycling the absolute excercise intensity was higher for the young men than for the older men due to the difference in corresponding maximal values. During arm-cranking there were no significant differences in the physiological responses between the age groups except that a higher ventilatory response was noted among the older compared to the young men. During leg-cycling the heart rate values were higher among the young compared to the older men. But, when the heart rate values were expressed as a percentage of maximal heart rate in the corresponding maximal tests, no significant differences between the age groups were found. The results indicated that 30-min of arm or leg exercise at the same relative submaximal excercise intensity produces a similar degree of physiological strain in healthy older compared to young men. During arm-cranking, the young and the older men exercised at the same external intensity, indicating a similar ability to perform prolonged excercise using smaller muscle groups expressed both in absolute and relative terms. Accepted: 7 October 1996     

Genotoxicity and PAC analysis of particulate and vapour phases of environmental tobacco smoke

Samples of indoor air were collected from an office room (88 m3) both before smoking and during experimental smoking of 96 cigarettes by 10 persons within 6 h. The particulates were collected on glass-fibre filters and the vapour-phase compounds on XAD-2 resin. The samples were extracted with acetone and analysed quantitatively for polycyclic aromatic compounds and qualitatively with GC-MS. The extracts of filters and XAD-2 resins were fractionated into neutral/acidic and 2 basic (strong and weak bases) fractions; all these fractions were tested with the sister-chromatid exchange (SCE) assay in Chinese hamster ovary (CHO) cells and with the Salmonella/microsome test (strain TA98). Total concentrations of PAC were 205 ng/m3 in the background sample and 1207 ng/m3 after contamination by cigarette smoking. The total PAC concentrations were 4-6 times higher in the vapour phase than in the particulate phase. The fractions of the particulate samples collected before smoking showed mainly marginal genotoxic activity, whereas after smoking their genotoxicity increased dramatically. The fractions of the vapour phase samples were not genotoxic before smoking, but after smoking the neutral/acidic and strong basic fractions induced responses in both assays. The SCE assay was more sensitive towards the vapour-phase mutagens of environmental tobacco smoke (ETS). The relative responses of the two basic fractions, whereas the fraction containing neutral and acidic compounds was the most potent in the SCE assay. In the Salmonella test, the mutagenic activity was mainly detected with metabolic activation, while the induction of SCE in CHO cells was also seen without an exogenous metabolic activation system.