Correction to: Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps.

The article Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps written by N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli,Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup.

Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps.

Dairy products are included in dietary guidelines worldwide, as milk, yoghurt, and cheese are good sources of calcium and protein, vital nutrients for bones and muscle mass maintenance. Bone growth and mineralization occur during infancy and childhood, peak bone mass being attained after early adulthood. A low peak bone mass has consequences later in life, including increased risk of osteoporosis and fractures. Currently, more than 200 million people worldwide suffer from osteoporosis, with approximately 9 million fractures yearly. This poses a tremendous economic burden on health care. Between 5% and 10% of the elderly suffer from sarcopenia, the loss of muscle mass and strength, further increasing the risk of fractures due to falls. Evidence from interventional and observational studies support that fermented dairy products in particular exert beneficial effects on bone growth and mineralization, attenuation of bone loss, and reduce fracture risk. The effect cannot be explained by single nutrients in dairy, which suggests that a combined or matrix effect may be responsible similar to the matrix effects of foods on cardiometabolic health. Recently, several plant-based beverages and products have become available and marketed as substitutes for dairy products, even though their nutrient content differs substantially from dairy. Some of these products have been fortified, in efforts to mimic the nutritional profile of milk, but it is unknown whether the additives have the same bioavailability and beneficial effect as dairy. We conclude that the dairy matrix exerts an effect on bone and muscle health that is more than the sum of its nutrients, and we suggest that whole foods, not only single nutrients, need to be assessed in future observational and intervention studies of health outcomes. Furthermore, the importance of the matrix effect on health outcomes argues in favor of making future dietary guidelines food based.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Lifestyle, anthropometric, socio-demographic and perinatal correlates of early adolescence hypertension: The Healthy Growth Study.

BACKGROUND AND AIMS: Various lifestyle, anthropometric, socio-demographic and perinatal characteristics have been separately associated with elevated blood pressure in children and adolescents. The aim of this study was to simultaneously evaluate all potential risk factors and to identify the most dominant correlates of early adolescence hypertension in a large group of school children 9-13 years old. METHODS AND RESULTS: A cross-sectional study with 1444 schoolchildren 9-13 years old, having full data on lifestyle, anthropometric, socio-demographic and perinatal indices, as well as blood pressure measurements. Early adolescents born large for their gestational age (LGA) (OR, 95% C.I. 0.49 (0.25-0.97)), those with higher levels of moderate to vigorous physical activity (MVPA) (OR, 95% C.I. 0.71 (0.53-0.96)) and those of a higher socioeconomic status (SES) (OR, 95% C.I. 0.51 (0.33-0.79)), had lower risk of hypertension, compared with their counterparts with appropriate birth weight, low levels of PA and with low SES respectively, independently of the variables used in the multivariate model. On the other hand, overweight and obese early adolescents (OR, 95% C.I. 2.61 (1.88-3.62)), those with central obesity (OR, 95% C.I. 1.75 (1.12-2.73)) and those having a hypertensive father (OR, 95% C.I. 1.93 (1.20-3.12)) had higher risk of hypertension compared with normal weight early adolescents and those without a family history of hypertension. CONCLUSIONS: Among the parameters examined, early adolescence abnormal body weight and central obesity, low PA, non LGA, low SES family and family history of hypertension were found to be independently associated with higher risk of hypertension. The identified correlates of early adolescence hypertension can be used by public health initiatives for early detection and management of this major public health problem, prioritizing early adolescents and families at the highest possible risk for hypertension.

Effects of hunger state on the brain responses to food cues across the life span.

The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently. We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated. Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state. The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span.

Correlates of ideal cardiovascular health in European adolescents: The HELENA study.

BACKGROUND AND AIMS: The ideal cardiovascular health (iCVH) construct consists of 4 health behaviors (smoking status, body mass index, physical activity and diet) and 3 health factors (total cholesterol, blood pressure and fasting glucose). A greater number of iCVH components in adolescence are related to better cardiovascular health, but little is known about the correlates of iCVH in adolescents. Thus, the aim of the study was to examine correlates of iCVH in European adolescents. METHODS AND RESULTS: The study comprised 637 European adolescents with complete iCVH data. Participants were part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional, multicenter study conducted in 9 different European countries. Correlates investigated were sex and age, family affluence scale, maternal education, geographic location, sleep time, television viewing, duration of pregnancy, birth weight and breastfeeding. Younger adolescents, those whose mothers had medium/high education or those who watched television less than 2 h per day had a greater number of iCVH components compared to those who were older, had a mother with low education or watched television 2 h or more daily (P ≤ 0.01). CONCLUSION: Since in our study older adolescents had worse iCVH than younger adolescents, early promotion of cardiovascular health may be important. Future studies may also investigate the usefulness of limiting television viewing to promote iCVH. Finally, since adolescents of mothers with low education had poorer iCVH, it may be of special interest to tailor public health promotion to adolescents from families with low socioeconomic status.

Inflammation in metabolically healthy and metabolically abnormal adolescents: The HELENA study.

BACKGROUND AND AIMS: Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index (BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI. METHODS AND RESULTS: A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed. RESULTS: Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status. CONCLUSIONS: Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently.

Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

Ideal cardiovascular health and inflammation in European adolescents: The HELENA study.

BACKGROUND AND AIMS: Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents. METHODS AND RESULTS: As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls. CONCLUSION: Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention.

Dietary fat intake modifies the influence of the FTO rs9939609 polymorphism on adiposity in adolescents: The HELENA cross-sectional study.

BACKGROUND AND AIMS: The fat mass and obesity associated gene (FTO) has been associated with obesity and dietary intake. The aims were: (i) To assess whether energy and macronutrient intakes were different across the FTOrs9939609 genotypes in adolescents, and (ii) to explore whether dietary fat intake modified the association of the rs9939609 polymorphism with adiposity. METHODS AND RESULTS: The FTOrs9939609 polymorphism was genotyped in 652 adolescents (53% females, 14.8 ± 1.2 years, TT = 246, TA = 296, AA = 110). Energy and macronutrient intake were assessed by two non-consecutive 24 h-recalls. Weight, height, waist circumference and skinfold thicknesses were measured and body fat percent was calculated. Energy and macronutrient intake were similar across the FTOrs9939609 genotypes (P > 0.2). There were significant interactions between the FTO polymorphism and fat intake on adiposity estimates (P < 0.05). In adolescents whose fat intake was below 30% (N = 203), the A allele of rs9939609 was not associated with adiposity indices. In contrast, in adolescents whose fat intake was between 30% and 35% of energy (N = 190), the rs9939609 polymorphism was associated with a 1.9% higher body fat per risk allele (95%CI: 0.39, 3.33; P < 0.05), and in those whose fat intake was higher than 35% (N = 259), it was associated with a 2.8% higher body fat per risk allele (95%CI: 1.27, 4.43; P < 0.001). CONCLUSIONS: These findings support the concept that the deleterious effect of the FTOrs9939609 polymorphism on adiposity is exacerbated in adolescents consuming high fat diets. In contrast, the consumption of low fat diets (<30% of energy) may attenuate the genetic predisposition to obesity in risk allele carriers.

Association of heart rate and blood pressure among European adolescents with usual food consumption: The HELENA study.

BACKGROUND AND AIM: In adults, there is some evidence that improving diet reduces blood pressure (BP) and the subsequent risk of cardiovascular diseases (CVDs). However, studies that analyse this association in adolescents are still scarce. The objective of the present study was to examine the associations between heart rate, systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) among European adolescents and usual intake of vegetables, fruits, dairy products, meat, fish, high-sugar foods and savoury snacks. METHODS AND RESULTS: In total, 2283 adolescents from the HELENA-study (12.5-17.5 years old; 1253 girls) were included. Dietary intake was assessed using two computerized 24-hour dietary recalls. Age, sex, body mass index, maternal educational level, physical activity and Tanner stage were considered as confounders. Associations were examined by mixed model analysis stratified by sex. Tests for trend were assessed by tertiles of intake while controlling for the aforementioned confounders. Dairy products and fish intake were negatively associated with BP and heart rate. Significant decreasing trends were observed for heart rate and BP across tertiles of dairy products, fish intake and high-sugar foods intake (p < 0.05). Significant increasing trends were observed for SBP and MAP across tertiles of savoury snack intake (p < 0.05). CONCLUSION: Significant but small inverse associations between fish and dairy products consumption with blood pressure and heart rate have been found in European adolescents. Dietary intervention studies are needed to explore these associations in the context of the modification of several risk factors for the prevention of cardiovascular diseases.

Occurrence and duration of various operational definitions of sedentary bouts and cross-sectional associations with cardiometabolic health indicators: the ENERGY-project.

OBJECTIVE: This study examined the occurrence and duration of sedentary bouts and explored the cross-sectional association with health indicators in children applying various operational definitions of sedentary bouts. METHODS: Accelerometer data of 647 children (10-13 years old) were collected in five European countries. We analyzed sedentary time (<100 cpm) accumulated in bouts of at least 5, 10, 20 or 30 min based on four operational definitions, allowing 0, 30 or 60s ≥100 cpm within bouts. Health indicators included anthropometrics (i.e. waist circumference and body mass index (BMI)) and in a subsample from two European countries (n=112) fasting capillary blood levels of glucose, C-peptide, high-density- and low-density cholesterol, and triglycerides. Data collection took place from March to July 2010. Associations were adjusted for age, gender, moderate-to-vigorous physical activity, total wear time and country. RESULTS: Occurrence of sedentary bouts varied largely between the various definitions. Children spent most of their sedentary time in bouts of ≥5 min while bouts of ≥20 min were rare. Linear regression analysis revealed few significant associations of sedentary time accumulated in bouts of ≥5-30 min with health indicators. Moreover, we found that more associations became significant when allowing no tolerance time within sedentary bouts. CONCLUSION: Despite a few significant associations, we found no convincing evidence for an association between sedentary time accumulated in bouts and health indicators in 10-13 year old children.

Revised Healthy Lifestyle-Diet Index and associations with obesity and iron deficiency in schoolchildren: The Healthy Growth Study.

BACKGROUND: The Healthy Lifestyle-Diet Index (HLD-index), previously developed to assess the degree of adherence to dietary and lifestyle guidelines for primary schoolchildren, was revised according to updated recommendations. Τhe association of the revised HLD-index (R-HLD-index) with obesity and iron deficiency (ID) was also examined. METHODS: A representative sample of 2660 primary schoolchildren from Greece (9-13 years old) participating in the 'Healthy Growth Study' was examined. Twelve components related to dietary and lifestyle patterns were used to develop the R-HLD-index. Scores from 0 up to 4 were assigned to each one of these components, giving a total score ranging from 0 to 48. The associations between the R-HLD-index, obesity and ID were examined via logistic regression analysis. RESULTS: The total score of the R-HLD-index calculated for each one of the study participants was found to range between 2 and 32 units, with higher scores being indicative of a healthier lifestyle and better diet quality. After adjusting for potential confounders, logistic regression analysis showed that an increase in the R-HLD-index score by one unit was associated with 6% lower odds for obesity. However, no significant association was observed between the R-HLD-index score and ID. CONCLUSIONS: The R-HLD-index may be a useful tool for public health policy makers and healthcare professionals when assessing diet quality and lifestyle patterns of primary schoolchildren. Identification of children with lower scores in the R-HLD-index and its individual components could guide tailored made interventions targeting specific children and behaviors.

Influence of parental socio-economic status on diet quality of European adolescents: results from the HELENA study.

Diet quality is influenced by socio-economic and geographical factors. The present study sought to assess whether adolescents' diet quality is affected by their parents' socio-economic status and whether the relationship between these factors is similar in northern and southern Europe. Data collected in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study in eight European countries were analysed. Dietary intake data were recorded via repeated 24 h recalls (using specifically developed HELENA Dietary Intake Assessment Tool software) and converted into an adolescent-specific Diet Quality Index (DQI-AM). Socio-economic status was estimated through parental educational level (Par-Educ-Lev) and parental occupation level (Par-Occ-Lev) as reported by the adolescents in a specific questionnaire. The DQI-AM data were then analysed as a function of Par-Educ-Lev and Par-Occ-Lev in northern European countries (Austria, Belgium, France, Germany and Sweden) and southern European countries (Greece, Italy and Spain). We studied a total of 1768 adolescents (age 14.7 (SD 1.3) years; percentage of girls: 52.8%; 1135 and 633 subjects from northern and southern Europe, respectively). On average, the DQI-AM score was higher in southern Europe than in northern Europe (69.1 (SD 0.1) v. 60.4 (SD 2.8), respectively; P < 0.001; Δ = 12.6%). The DQI was positively correlated with both paternal and maternal Par-Educ-Lev. However, this association was more pronounced in northern Europe than in southern Europe (P interaction = 0.004 for the mother and 0.06 for the father). The DQI was also positively correlated with Par-Occ-Lev (all P trends < 0.01), but this correlation was independent of the geographical area (P interaction = 0.51 for the mother and 0.50 for the father). In conclusion, Par-Educ-Lev and Par-Occ-Lev are associated with diet quality in adolescents in Europe. However, this association differs between northern Europe and southern Europe.

Mechanisms of stress, energy homeostasis and insulin resistance in European adolescents--the HELENA study.

BACKGROUND AND AIMS: Stress is hypothesized to facilitate the development of obesity, whose the foundations are already set during childhood and adolescence. We investigated the relationship between the stress-system, selected mechanisms of energy homeostasis and insulin resistance (IR) in a sample of European adolescents. METHODS AND RESULTS: Within HELENA-CSS, 723 adolescents (12.5-17.5 years) from 10 European cities provided all the necessary data for this study. Fasting blood samples were collected for cortisol, leptin, insulin and glucose analysis. HOMA-IR was calculated from insulin and glucose concentrations. Adolescents' body fat (BF) %, age and duration of exclusive breastfeeding were assessed. For boys and girls separately, the relationship of cortisol with leptin, insulin, glucose and HOMA-IR was examined by computing Pearson correlation coefficients and Hierarchical Linear Models (HLMs), with 'city' as cluster unit, adjusting for age, BF% and duration of exclusive breastfeeding. In boys, Pearson correlation coefficients illustrated positive correlations of cortisol with insulin (r = 0.144; p = 0.013), glucose (r = 0.315; p < 0.001) and HOMA-IR (r = 0.180; p = 0.002), whilst in girls, this positive relationship was observed for leptin (r = 0.147; p = 0.002), insulin (r = 0.095; p = 0.050) and HOMA-IR (r = 0.099; p = 0.041), but not for glucose (r = 0.054; p = 0.265). Observed associations were independent of adolescents' age, BF% and duration of exclusive breastfeeding after computing HLMs. CONCLUSION: This study suggests that the stress-system is positively related to mechanisms of energy homeostasis and IR in European adolescents, and reveals a potential small gender difference in this relationship. The hypothesis that stress might facilitate the development of obesity during adolescence is supported.

Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet.

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.

Conception via in vitro fertilization and delivery by Caesarean section are associated with paediatric asthma incidence.

BACKGROUND: The association between perinatal factors and asthma inception is under rigorous investigation. Nevertheless, evidence of a correlation between asthma, conception via in vitro fertilization (IVF) and delivery through Caesarean section (C-section) is inconclusive. OBJECTIVE: We aimed to assess the relation of asthma incidence with IVF and C-section, after controlling for several potential confounding factors. METHODS: Parent-reported wheeze in the last 12 months (current), wheeze ever, physician-diagnosed asthma, method of conception, and type of delivery were recorded from questionnaires filled in by the parents of 2016 Greek children aged 9-13, (the Healthy Growth Study population). Some perinatal data were recorded from children's medical records and others were reported by parents; anthropometric measurements were also conducted in children. RESULTS: IVF was correlated with physician-diagnosed asthma (OR = 2.25; 95% CI = 1.11-4.56), but not with current/ever wheeze after adjustment for potential confounding factors. After adjustment, C-section was also associated with asthma (OR = 1.39; 95% CI = 1.04-1.87), but not with current/ever wheeze. When the association of both IVF and C-section with asthma was examined in the same multivariate logistic regression model, it was weakened to borderline significance (OR = 2.04; 95% CI = 1-4.15 and OR = 1.34; 95% CI = 1-1.81 respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Conception via IVF and delivery by C-section may predispose children to future asthma development. Either variable could also exert a confounding effect on the link of the other to asthma; this may partially be accountable for inconsistencies in the findings of pertinent studies.

The obesity-asthma link in different ages and the role of body mass index in its investigation: findings from the Genesis and Healthy Growth Studies.

BACKGROUND: To date, an obesity/asthma link is well defined in adults; however, the nature of such a link is obscure in children, partly due to Body Mass Index (BMI) limitations as a surrogate fat mass marker in childhood. We thus opted to investigate the association of adiposity with asthma in children of different ages, using several indices to assess fat mass. METHODS: Wheeze ever/in the last 12 months (current) and physician-diagnosed asthma were retrospectively reported via questionnaire by the parents of 3641 children, participating in two cross-sectional studies: 1626 children aged 2-5 (the Genesis Study) and 2015 children aged 9-13 (the Healthy Growth Study). Perinatal data were recorded from the children's medical records or reported by parents. Anthropometric measurements (i.e., BMI, waist/hip circumference, biceps/triceps/subscapular/suprailiac skinfold thickness) were conducted in both cohorts; bioelectric impedance analysis (BIA) was conducted only in preadolescent children. RESULTS: In children aged 2-5, asthma was positively correlated with conicity index, waist/hip circumference, waist-to-height ratio, skinfold thickness, and skinfold-derived percentage fat mass (P < 0.05) but not BMI or BMI-defined overweight/obesity, after adjusting for several confounders. In children aged 9-13, asthma was positively associated with conicity index, waist circumference, waist-to-height ratio, skinfold thickness, skinfold-derived percentage fat mass, BIA-derived percentage fat mass, BMI, and BMI-defined overweight/obesity, following adjustment (P < 0.05). Current/ever wheeze was not consistently associated with fat mass in either population. CONCLUSIONS: Fat mass is positively linked to asthma in both 2-5 and 9-13 age spans. However, the failure of BMI to correlate with preschool asthma suggests its potential inefficiency in asthma studies at this age range.