Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children.

BACKGROUND: The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index. METHODS: In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD). RESULTS: The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012). CONCLUSIONS: This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.

Exposure to subliminal arousing stimuli induces robust activation in the amygdala, hippocampus, anterior cingulate, insular cortex and primary visual cortex: a systematic meta-analysis of fMRI studies.

Functional Magnetic Resonance Imaging (fMRI) demonstrates that the subliminal presentation of arousing stimuli can activate subcortical brain regions independently of consciousness-generating top-down cortical modulation loops. Delineating these processes may elucidate mechanisms for arousal, aberration in which may underlie some psychiatric conditions. Here we are the first to review and discuss four Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies using subliminal paradigms. We find a maximum of 9 out of 12 studies using subliminal presentation of faces contributing to activation of the amygdala, and also a significantly high number of studies reporting activation in the bilateral anterior cingulate, bilateral insular cortex, hippocampus and primary visual cortex. Subliminal faces are the strongest modality, whereas lexical stimuli are the weakest. Meta-analyses independent of studies using Regions of Interest (ROI) revealed no biasing effect. Core neuronal arousal in the brain, which may be at first independent of conscious processing, potentially involves a network incorporating primary visual areas, somatosensory, implicit memory and conflict monitoring regions. These data could provide candidate brain regions for the study of psychiatric disorders associated with aberrant automatic emotional processing.

Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children.

OBJECTIVE: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-ß-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men. DESIGN: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children. RESULTS: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038). CONCLUSION: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.

Characterization of the neuropeptide Y system in the frog Silurana tropicalis (Pipidae): three peptides and six receptor subtypes.

Neuropeptide Y and its related peptides PYY and PP (pancreatic polypeptide) are involved in feeding behavior, regulation of the pituitary and the gastrointestinal tract, and numerous other functions. The peptides act on a family of G-protein coupled receptors with 4-7 members in jawed vertebrates. We describe here the NPY system of the Western clawed frog Silurana (Xenopus) tropicalis. Three peptides, NPY, PYY and PP, were identified together with six receptors, namely subtypes Y1, Y2, Y4, Y5, Y7 and Y8. Thus, this frog has all but one of the ancestral seven gnathostome NPY-family receptors, in contrast to mammals which have lost 2-3 of the receptors. Expression levels of mRNA for the peptide and receptor genes were analyzed in a panel of 19 frog tissues using reverse transcriptase quantitative PCR. The peptide mRNAs had broad distribution with highest expression in skin, blood and small intestine. NPY mRNA was present in the three brain regions investigated, but PYY and PP mRNAs were not detectable in any of these. All receptor mRNAs had similar expression profiles with high expression in skin, blood, muscle and heart. Three of the receptors, Y5, Y7 and Y8, could be functionally expressed in HEK-293 cells and characterized with binding studies using the three frog peptides. PYY had the highest affinity for all three receptors (K(i) 0.042-0.34 nM). Also NPY and PP bound to the Y8 receptor with high affinity (0.14 and 0.50 nM). The low affinity of NPY for the Y5 receptor (100-fold lower than PYY) differs from mammals and chicken. This may suggest a less important role of NPY on Y5 in appetite stimulation in the frog compared with amniotes. In conclusion, our characterization of the NPY system in S. tropicalis with its six receptors demonstrates not only greater complexity than in mammals but also some interesting differences in ligand-receptor preferences.

Associations between severity of obesity in childhood and adolescence, obesity onset and parental BMI: a longitudinal cohort study.

OBJECTIVE: To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents. DESIGN: Longitudinal cohort study. SUBJECTS: Obese children (n = 231) and their parents (n = 462) from the Swedish National Childhood Obesity Centre. METHODS: Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment. RESULTS: For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P = 0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P < 0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents. CONCLUSION: The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing.

In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

Following the identification of the C-C chemokines RANTES, MIP-1alpha and MIP-1beta as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1alpha and MIP-1 receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains and by simian immunodeficiency virus (SIV), whereas CXCR4, a receptor for the C-X-C chemokine SDF-1, is used by MT2-tropic HIV-1 and HIV-2, but not by SIV. Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain of gp120 were associated with the loss of sensitivity to C-C chemokines and the shift in co-receptor usage. These results suggest an adaptive evolution of HIV-1 in vivo, leading to escape from the control of the antiviral C-C chemokines.

Sweden beyond oil: the efficient use of energy.

Technology now being introduced in industry, buildings, and transportation is much more energy-efficient than today's average technology. Changes in production and consumption are tending to decrease the intensity of energy use. By applying available economic technology, it may be possible to reduce energy use in Sweden from the present 1400 petajoules per year to about 900 petajoules per year soon after the turn of the century, even with a 50 percent increase in the consumption of goods and services. Technology now being developed could reduce energy demand even further.

Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.

BACKGROUND: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.

Elevated total plasma-adiponectin is stable over time in young women with bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is characterized by dysregulated eating behaviour and present data suggest adipokines may regulate food intake. We investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women with BN. METHODS: The study was designed as a cross-sectional study with a longitudinal arm for patients with BN. Plasma-adiponectin and leptin was measured in 148 female patients seeking psychiatric ambulatory care and 45 female controls. Fifteen patients were diagnosed with BN and the remaining with other affective and anxiety disorders. P-adiponectin and P-leptin levels were compared between patients with BN, patients without BN and controls. At follow-up 1-2years later, adipokines were reassessed in patients with BN and the Eating Disorder Examination Questionnaire was used to assess symptom severity. RESULTS: P-adiponectin was elevated in patients with BN at baseline and at follow-up when compared to patients without BN and controls (P<0.004 and <0.008 respectively). The difference remained significant after controlling for body mass index. P-adiponectin was correlated to symptom severity at follow-up in patients with BN without morbid obesity (ρ=0.72, P<0.04). P-leptin-adiponectin-ratio was significantly lower in patients with BN compared to controls (P<0.04) and P-leptin non-significantly lower. CONCLUSIONS: Findings indicate a stable elevation of P-adiponectin in women with BN. P-adiponectin at follow-up correlates to eating disorder symptom severity in patients without morbid obesity, indicating that P-adiponectin should be further investigated as a possible potential prognostic biomarker for BN.

Cloning and characterization of a zebrafish Y2 receptor.

The NPY receptors belong to the superfamily of G-protein coupled receptors and in mammals this family has five members, named Y1, Y2, Y4, Y5, and Y6. In bony fish, four receptors have been identified, named Ya, Yb, Yc and Y7. Yb and Y7 arose prior to the split between ray-fined fishes and tetrapods and have been lost in mammals. Yc appeared as a copy of Yb in teleost fishes. Ya may be an ortholog of Y4, but surprisingly no unambiguous receptor ortholog to any of the mammalian subtypes has yet been identified in bony fishes. Here we present the cloning and pharmacological characterization of a Y2 receptor in zebrafish, Danio rerio. To date, this is the first Y2 receptor outside mammals and birds that has been characterized pharmacologically. Phylogenetic analysis and synteny confirmed that this receptor is orthologous to mammalian Y2. We show that the receptor is pharmacologically most similar to chicken Y2 which leads to the conclusion that Y2 has acquired several novel characteristics in mammals. Y2 from zebrafish binds very poorly to the Y2-specific antagonist BIIE0246. Our pharmacological characterization supports our previous conclusions regarding the binding pocket of BIIE0246 in the human Y2 receptor.

Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.

Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting.

The ancestry of the prolactin-releasing hormone precursor.

The prolactin-releasing hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C-terminal RF-motif, also present in the neuropeptide FF and the neuropeptide RF amide-related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C-RF amide in chicken, shedding light on the PRH ancestry.

High species variation within the repertoire of trace amine receptors.

Using a variety of search strategies, we obtained the complete or nearly complete repertoire of trace amine receptors from humans, mice, rats, zebrafish, pufferfish, and a number of invertebrates. We found that the number of functional receptors varies from 5 to 50 in each genome, showing that this family of GPCRs has a very dynamic gene repertoire. We show that the previously cloned and characterized GPCRs from insects and mollusks are more closely related to mammalian serotonin, dopamine, and adrenalin receptors than to mammalian TA receptors. This suggests that the ability to bind TAs has arisen independently in different developmental lineages.

Feather pecking in chickens is genetically related to behavioural and developmental traits.

Feather pecking (FP) is a detrimental behaviour in chickens, which is performed by only some individuals in a flock. FP was studied in 54 red junglefowl (ancestor of domestic chickens), 36 White Leghorn laying hens, and 762 birds from an F(2)-intercross between these two lines. From all F(2)-birds, growth and feed consumption were measured. Age at sexual maturity and egg production in females, and corticosterone levels in males were also measured. From 333 F(2)-birds of both sexes, and 20 parental birds, body composition with respect to bone mineral content, muscle and fat was obtained by post-mortem examinations using Dual X-Ray Absorptiometry (DXA). In femurs of the same birds, the bone density and structure were analysed using DXA and Peripheral Quantitative Computerized Tomography (pQCT), and a biomechanical analysis of bone strength was performed. Furthermore, plumage condition was determined in all birds as a measure of being exposed to feather pecking. Using 105 DNA-markers in all F(2)-birds, a genome-wide scan for Quantitative Trait Loci (QTL), associated with the behaviour in the F(2)-generation was performed. FP was at least as frequent in the red junglefowl as in the White Leghorn strain studied here, and significantly more common among females both in the parental strains and in the F(2)-generation. In the F(2)-birds, FP was phenotypically linked to early sexual maturation, fast growth, weak bones, and, in males, also high fat accumulation, indicating that feather peckers have a different resource allocation pattern. Behaviourally, F(2) feather peckers were more active in an open field test, in a novel food/novel object test, and in a restraint test, indicating that feather pecking might be genetically linked to a proactive coping strategy. Only one suggestive QTL with a low explanatory value was found on chromosome 3, showing that many genes, each with a small effect, are probably involved in the causation of feather pecking. There were significant effects of sire and dam on the risk of being a victim of feather pecking, and victims grew faster pre- and post-hatching, had lower corticosterone levels and were less active in a restraint test. Hence, a wide array of behavioural and developmental traits were genetically linked to FP.

Cotransfection of HIV-1 molecular clones with restricted cell tropism may yield progeny virus with altered phenotype.

Seven infectious molecular clones were obtained from a human immunodeficiency virus type 1 isolate with rapid/high replicative capacity. Biological characterization of progeny viruses obtained after transfection of clones into peripheral blood mononuclear cells showed that six clones yielded virus with restricted cell tropism, whereas one clone yielded virus able to replicate in cell lines. Although transfection of each of the clones 12, 13, and 82 individually gave rise to viruses with restricted tropism, viruses recovered from cotransfection of the mixtures of these clones exhibited altered phenotype, inasmuch as they were able to replicate in cell lines. To test whether recombination and/or complementation has taken place in the mixture of clones 12 + 13 + 82, the progeny virus was diluted to end point in 15 parallel series. Viruses with diverse biological phenotypes were recovered. With the help of distinctive restriction enzyme markers in regions comprising the vpu/env junction and variable regions 4 and 5 (V4/V5) of the env gene, recombinant genotypes could be identified with high frequency. No particular biological phenotype could be linked to a certain genotype in this study. The results show that different coexisting variants may interact and thereby influence the biological phenotype of a viral population.

Neuropeptide Y receptor subtype with unique properties cloned in the zebrafish: the zYa receptor.

Neuropeptide Y (NPY) belongs to a family of structurally related neuroendocrine peptides for which five different G-protein-coupled receptor subtypes have been cloned in mammals. To identify additional subtypes we have performed PCR with degenerate primers in different species. We describe here the cloning and pharmacological profile of a unique NPY receptor subtype in the zebrafish that has tentatively been called the zYa receptor. It has 46-50% amino acid identity to the mammalian Y1, Y4 and y6 receptors and the previously cloned zebrafish receptors zYb and zYc, and only about 27% to Y2 and Y5. The zYa receptor binds NPY and PYY from mammals as well as zebrafish with high affinities and has a K(d) of 28 pM for porcine (125)I-PYY. It has a unique binding profile displaying some features in common with each of the mammalian Y1, Y2 and Y5 receptors. In a microphysiometer assay the receptor responds with extracellular acidification. Chromosomal mapping in the zebrafish genome of zYa, zYb and zYc receptor genes indicates a possible orthologous relationship between zYc and mammalian y6, but identifies no obvious mammalian ortholog for zYa (zYb is a recent copy of zYc in the fish lineage). These results imply that previous studies of NPY in fishes, which have striven to interpret the effects within the framework of mammalian Y1, Y2, and Y5 receptors, need to be reevaluated. Thus, the sequence comparisons, pharmacological properties, and chromosomal localization suggest that the zYa receptor is a novel NPY receptor subtype which is likely to be present also in mammals.

How crash severity in rear impacts influences short- and long-term consequences to the neck.

The main public-health problem concerning WAD are injuries leading to long-term consequences. Yet epidemiological studies mostly concentrate on data based on the injury outcome occurring shortly after the crash. The purpose of this article is to study the influence of crash severity in rear impacts leading to short and long-term consequences to the neck (WAD 1-3), lasting less than or more than 1 year. The influence of change of velocity as well as the car acceleration were investigated by using data from crash pulse recorders (CPR) installed in vehicles, involved in rear impacts. The influence of the car acceleration were also investigated by studying the frequency of occurrence of a tow-bar (hinge) on the struck car. Apart from real-life data, full-scale car-to-car crashes were performed to evaluate the influence of a tow-bar on the struck car. The crash tests showed that a tow-bar may significantly affect the acceleration of the car as well as that of the occupant. According to real-life crashes, a tow-bar on the struck car increased the risk of long-term consequences by 22% but did not affect the risk of short-term consequences. Out of the 28 crash recorder-equipped struck cars involving 38 occupants, 15 sustained no injury where the peak acceleration was 6g or less, 20 sustained short-term consequences where the peak acceleration was 10g or less. Three occupants from two different crashes sustained long-term consequences. The two crashes which resulted in long-term disabling neck injuries had the highest peak acceleration (15 and 13 x g), but not the highest change of velocity.

Comparison of car seats in low speed rear-end impacts using the BioRID dummy and the new neck injury criterion (NIC).

Long-term whiplash associated disorders (WAD) 1-3 sustained in low velocity rear-end impacts is the most common disability injury in Sweden. Therefore, to determine neck injury mechanisms and develop methods to measure neck-injury related parameters are of importance for current crash-safety research. A new neck injury criterion (NIC) has previously been proposed and evaluated by means of dummy, human and mathematical rear-impact simulations. So far, the criterion appears to be sensitive to the major car and collision related risk factors for injuries with long-term consequences. To further evaluate the applicability of NIC, four seats were tested according to a recently proposed sled-test procedure. 'Good' as well as 'bad' seats were chosen on the basis of a recently presented disability risk ranking list. The dummy used in the current tests was the Biofidelic Rear Impact Dummy (BioRID). The results of this study showed that NICmax values were generally related to the real-world risk of long-term WAD 1-3. Furthermore, these results suggested that NICmax calculated from sled tests using the BioRID dummy can be used for evaluating the neck injury risk of different car seats.

The impact of intronic single nucleotide polymorphisms and ethnic diversity for studies on the obesity gene FTO.

In 2007, the first common genetic variants were identified, which undoubtedly affect our susceptibility to obesity. These variants are located in the fat mass and obesity-associated gene FTO. Since then, over 50 loci for common obesity have been identified. As the research on these loci is still at an early stage, there is a great need to review, for clarification purposes, the current research on FTO, as this is likely to influence future studies. Based on the current knowledge, FTO seems to be directly involved in the regulation of energy intake, but there is an urgent need for the identification of regulatory polymorphisms. Thus, herein, we discuss current knowledge and highlight putative functional regions in FTO based on published data and computer-based analysis.