Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

The healthy Nordic diet predicts muscle strength 10 years later in old women, but not old men.

Background: a number of nutrients have been found to be associated with better muscle strength and mass; however, the role of the whole diet on muscle strength and mass remains still unknown. Objective: to examine whether the healthy Nordic diet predicts muscle strength, and mass 10 years later among men and women. Methods: about 1,072 participants belong to the Helsinki Birth Cohort Study, born 1934-44. Diet was assessed with a validated food-frequency questionnaire during 2001-04. The Nordic diet score (NDS) was calculated. The score included Nordic fruits, vegetables, cereals, ratio of polyunsaturated to saturated fatty acids, low-fat milk, fish, red meat, total fat and alcohol. Higher scores indicated better adherence to the healthy Nordic diet. Hand grip strength, leg strength (knee extension) and muscle mass were measured during the follow-up, between 2011 and 2013. Results: in women, each 1-unit increase in the NDS was related to 1.83 N greater leg strength (95% confidence interval [CI] 0.14-3.51; P = 0.034), and 1.44 N greater hand grip strength (95% CI: 0.04-2.84; P = 0.044). Women in the highest quartile of the NDS had on average 20.0 N greater knee extension results, and 14.2 N greater hand grip results than those in the lowest quartile. No such associations were observed among men. The NDS was not significantly related to muscle mass either in men or women. Conclusions: adherence to the healthy Nordic diet seems to protect from weaker muscle strength in old women. Therefore, the healthy Nordic diet may help to prevent disability.

Objectively measured physical activity and physical performance in old age.

Background: physical performance is a key factor that determines how older people cope with daily tasks and maintain independency. There is strong evidence suggesting that physical activity (PA) is important in maintaining physical performance in old age. However, most studies have been done using self-reported PA. Our aim was to explore the association between objectively measured PA and physical performance in old age. Methods: we studied 695 participants (mean age 70.7 years, SD 2.7) from the Helsinki Birth Cohort Study. Physical performance was assessed with the Senior Fitness Test (SFT) and PA with a multisensory activity monitor SenseWear Pro 3 Armband. Results: total volume of PA was significantly associated with the overall SFT score (ß = 0.08; 95% confidence interval: 0.07-0.10, P < 0.001). There were no significant differences between men and women. Both light and moderate to vigorous level of PA were positively associated with the overall SFT score, while sedentary time was negatively associated with the overall SFT score. Conclusions: volume of objectively measured PA among older people was positively associated with the physical performance measured with a validated fitness test battery.

Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site.

Genome-wide association studies (GWAS) have identified hundreds of genetic variants that are associated with lipid phenotypes. However, data supporting a functional role for these variants in the context of lipid metabolism are scarce. We investigated the association of the lipoprotein lipase (LPL) variant rs13702 with plasma lipids and explored its potential for functionality. The rs13702 minor allele had been predicted to disrupt a microRNA (miR) recognition element (MRE) seed site (MRESS) for the human microRNA-410 (miR-410). Furthermore, rs13702 is in linkage disequilibrium (LD) with several SNPs identified by GWAS. We performed a meta-analysis across ten cohorts of participants that showed a statistically significant association of rs13702 with triacylglycerols (TAG) (p = 3.18 × 10(-42)) and high-density lipoprotein cholesterol (HDL-C) (p = 1.35 × 10(-32)) with each copy of the minor allele associated with 0.060 mmol/l lower TAG and 0.041 mmol/l higher HDL-C. Our data showed that an LPL 3' UTR luciferase reporter carrying the rs13702 major T allele was reduced by 40% in response to a miR-410 mimic. We also evaluated the interaction between intake of dietary fatty acids and rs13702. Meta-analysis demonstrated a significant interaction between rs13702 and dietary polyunsaturated fatty acid (PUFA) with respect to TAG concentrations (p = 0.00153), with the magnitude of the inverse association between dietary PUFA intake and TAG concentration showing -0.007 mmol/l greater reduction. Our results suggest that rs13702 induces the allele-specific regulation of LPL by miR-410 in humans. This work provides biological and potential clinical relevance for previously reported GWAS variants associated with plasma lipid phenotypes.

A healthy Nordic diet and physical performance in old age: findings from the longitudinal Helsinki Birth Cohort Study.

Epidemiological studies have shown that a number of nutrients are associated with better physical performance. However, little is still known about the role of the whole diet, particularly a healthy Nordic diet, in relation to physical performance. Therefore, we examined whether a healthy Nordic diet was associated with measures of physical performance 10 years later. We studied 1072 participants from the Helsinki Birth Cohort Study. Participants' diet was assessed using a validated 128-item FFQ at the mean age of 61 years, and a priori-defined Nordic diet score (NDS) was calculated. The score included Nordic fruits and berries, vegetables, cereals, PUFA:SFA and trans-fatty acids ratio, low-fat milk, fish, red and processed meat, total fat and alcohol. At the mean age of 71 years, participants' physical performance was measured using the Senior Fitness Test (SFT), and an overall SFT score was calculated. Women in the highest fourth of the NDS had on average 5 points higher SFT score compared with those in the lowest fourth (P for trend 0·005). No such association was observed in men. Women with the highest score had 17% better result in the 6-min walk test, 16% better arm curl and 20% better chair stand results compared with those with the lowest score (all P values<0·01). In conclusion, a healthy Nordic diet was associated with better overall physical performance among women and might help decrease the risk of disability in old age.

Early growth and postprandial appetite regulatory hormone responses.

Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34-69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.

Early growth and postprandial glucose, insulin, lipid and inflammatory responses in adulthood.

PURPOSE OF REVIEW: Epidemiological findings suggest that prenatal and postnatal growth is associated with later health outcomes including cardiovascular disease and type 2 diabetes. It has been suggested that these associations are mediated through classical risk factors, for example dyslipidemia. Despite extensive epidemiological investigations, only limited data are available on the long-term influences of early growth on postprandial responses, although postprandial levels of many risk factors have been proposed to be more important than fasting levels in disease process. This review focuses on recent studies evaluating the effect of early growth on postprandial responses. RECENT FINDINGS: Current evidence from postprandial studies shows that individuals who were small at birth or grew slowly during infancy have elevated postprandial insulin and triglyceride responses. However, early growth does not seem to affect postprandial inflammatory markers. It is likely that both liver programming and abnormalities in insulin-sensitive tissues play key roles in explaining these elevated responses. SUMMARY: Recent studies suggest that slow growth during early life has an adverse effect on postprandial metabolism, and predicts higher insulin and triglyceride responses. These elevated postprandial responses might be one underlying mechanism explaining the increased risk of cardiovascular disease and type 2 diabetes associated with nonoptimal early growth.

Impact of overweight and glucose tolerance on postprandial responses to high- and low-glycaemic index meals.

The beneficial effects of a low-glycaemic index (GI) meal on postprandial glucose and insulin levels have been demonstrated. However, limited data are available on the impact of overweight and glucose tolerance on postprandial responses to different GI meals. Our aim was to study the effects of physiological characteristics on postprandial glucose, insulin and lipid responses and the relative glycaemic response (RGR) of a low-GI (LGI) and a high-GI (HGI) meal. We recruited twenty-four normal-weight and twenty-four overweight subjects, twelve with normal glucose tolerance (NGT) and twelve with impaired glucose tolerance (IGT) in each group. Both test meals were consumed once and the glucose reference twice. Blood glucose and insulin were measured in the fasting state and over a 2 h period after each study meal, and TAG and NEFA were measured in the fasting state and over a 5 h period. The glucose responses of subjects with IGT differed significantly from those of subjects with NGT. The highest insulin responses to both meals were observed in overweight subjects with IGT. Physiological characteristics did not influence TAG or NEFA responses or the RGR of the meals. The LGI meal resulted in lower glucose (P < 0·001) and insulin (P < 0·001) responses, but higher TAG responses (P < 0·001), compared with the HGI meal. The GI of the meals did not affect the NEFA responses. In conclusion, the LGI meal causes lower glucose and insulin responses, but higher TAG responses, than the HGI meal. The RGR of the meals does not differ between normal-weight and overweight subjects with NGT or IGT.

Birth weight modifies the association between a healthy Nordic diet and office blood pressure in old age.

A healthy diet reduces risk for high blood pressure. A small body size at birth increases risk for high blood pressure. Our aim was to study whether birth weight modifies the association between a healthy Nordic diet, characterized by high intake of Nordic vegetables, fruits, and berries, whole-grain rye, oat, and barley, and rapeseed oil, and blood pressure. Finnish men and women (n = 960) born in 1934-1944 attended clinical visits including clinical measurements, and questionnaires in 2001-2004 and 2011-2013. Linear regression was applied to investigate the interactions between birth weight and Nordic diet (measured by the Baltic sea diet score (BSDS)) on blood pressure change during the 10-year follow-up. Baseline Nordic diet and birth weight showed a significant interaction on systolic blood pressure (SBP) (p = 0.02), and pulse pressure (PP) (p < 0.01) over a 10-year follow-up. In the lowest birth weight category (women < 2951 g, men < 3061 g), predicted SBP decreased across BSDS thirds (lowest (T1): 155 mmHg, highest (T3): 145 mmHg, p for linearity = 0.01) as did predicted PP (T1: 71 mmHg, T3: 63 mmHg, p < 0.01). In the middle birth weight category, predicted SBP increased across BSDS thirds (T1: 151 mmHg, T3: 155 mmHg, p = 0.02) as did predicted PP (T1: 67 mmHg, T3: 71 mmHg, p < 0.01). In the highest birth weight category, no associations were found. Higher adherence to a healthy Nordic diet was associated with lower SBP and PP in individuals with low birth weight but with higher SBP and PP in those with average birth weight.

Healthy diets and telomere length and attrition during a 10-year follow-up.

BACKGROUND: Telomeres are repeats of DNA that contain the sequence TTAGGG at the ends of each chromosome, and their function is to protect DNA from damage. Little evidence exists regarding the relationship between dietary patterns and telomere length, especially derived applying longitudinal design. The aim was to study if overall dietary pattern is associated with leukocyte telomere length (LTL) or faster telomere attrition or both. METHODS: The setting was longitudinal and observational. Participants were 456 men and 590 women whose birth settled in between 1934 and 1944 and who participated in the Helsinki Birth Cohort Study. Baltic sea diet score (BSDS), modified Mediterranean diet score (mMED), and dietary inflammatory index (DII®) were calculated based on a 128-item food frequency questionnaire (FFQ) collected in 2001-2004. LTL was measured twice, in 2001-2004 and in 2011-2013 by quantitative real-time polymerase chain reaction. Association between the dietary patterns and LTL were analysed by general linear models with appropriate contrasts. RESULTS: BSDS, mMED, and DII did not associate with LTL in the cross-sectional analysis in men or women. Higher mMED at baseline (2001-2004) was associated with slightly faster LTL shortening during the follow-up (standardized ß -0.08, 95% CI -0.15, -0.01). No association between mMED and LTL change was found in men. Adherence to BSDS and DII did not associate with LTL change in men or women. CONCLUSION: Baltic sea diet, Mediterranean diet, and diet's inflammatory potential seem to have only little impact on telomere length and telomere attrition in elderly Finnish men and women.

The Healthy Nordic Diet and Mediterranean Diet and Incidence of Disability 10 Years Later in Home-Dwelling Old Adults.

BACKGROUND/OBJECTIVE: Diet has a major impact on a person's health. However, limited information exists on the long-term role of the whole diet on disability. We investigated the association of the healthy Nordic diet and the Mediterranean diet with incident disability 10 years later. DESIGN: Longitudinal, with a follow-up of 10 years. SETTINGS/PARTICIPANTS: A total of 962 home-dwelling men and women from the Helsinki Birth Cohort Study, mean age 61.6 years, who were free of disability at baseline. MEASUREMENTS: At baseline, 2001-2004, the Nordic diet score (NDS) and modified Mediterranean diet score (mMDS) were calculated using a validated 128-item food-frequency questionnaire. Higher scores indicated better adherence to the diet. Participants' incident disability was assessed during 2011-2013 by a self-reported questionnaire and was based on mobility limitations and difficulties to perform self-care activities. Analyses were performed using logistic regression and adjusted for potential confounding factors. RESULTS: In total, 94 participants (9.8%) developed mobility limitations and 45 participants (4.7%) developed difficulties in self-care activities during 10 year follow-up. The likelihood of having mobility limitations (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.22-0.80) and difficulties in self-care activities (OR 0.38, 95% CI 0.15-0.94) were lower among those in the highest NDS tertile than among those in the lowest NDS tertile. Greater mMDS was associated with a lower disability incidence; however, the association was not statistically significant. CONCLUSIONS/IMPLICATIONS: Adherence to the healthy Nordic diet predicts 10-year incidence of mobility limitations and difficulties to perform self-care activities in old age and may thus be protective against disability in Nordic population.

Telomere length and physical performance among older people-The Helsinki Birth Cohort Study.

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.

New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

Body composition as a predictor of physical performance in older age: A ten-year follow-up of the Helsinki Birth Cohort Study.

BACKGROUND: This study assessed how different measures of body composition predict physical performance ten years later among older adults. METHODS: The participants were 1076 men and women aged 57 to 70 years. Body mass index (BMI), waist circumference, and body composition (bioelectrical impedance analysis) were measured at baseline and physical performance (Senior Fitness Test) ten years later. Linear regression analyses were adjusted for age, education, smoking, duration of the follow-up and physical activity. RESULTS: Greater BMI, waist circumference, fat mass, and percent body fat were associated with poorer physical performance in both sexes (standardized regression coefficient [ß] from -0.32 to -0.40, p < 0.001). Lean mass to BMI ratio was positively associated with later physical performance (ß = 0.31 in men, ß = 0.30 in women, p < 0.001). Fat-free mass index (lean mass/height2) in both sexes and lean mass in women were negatively associated with later physical performance. Lean mass residual after accounting for the effect of height and fat mass was not associated with physical performance. CONCLUSIONS: Among older adults, higher measures of adiposity predicted poorer physical performance ten years later whereas lean mass was associated with physical performance in a counterintuitive manner. The results can be used when appraising usefulness of body composition indicators for definition of sarcopenic obesity.

Food and nutrient intakes by temperament traits: findings in the Helsinki Birth Cohort Study.

BACKGROUND/OBJECTIVES: Previous studies have shown that the temperament traits are related to risk factors for chronic diseases, which could be partly explained by lifestyle habits. However, little is known whether temperament traits associate with diet. The aim of this study was to examine the cross-sectional associations between temperament traits and the whole diet. SUBJECTS/METHODS: We studied 1668 men and women, aged 56-70, from the Helsinki Birth Cohort Study. Temperament was measured using the Tridimensional Personality Questionnaire. Information on diet was collected by a validated 128-item food frequency questionnaire. The associations of temperament traits; novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (P), with diet were tested by linear regression analysis. RESULTS: After adjustment for potential confounders, greater HA was related to poorer diet quality, including lower consumption of vegetables, fruits, fish and several vitamins. RD was associated with healthier diet quality, including higher consumption of vegetables and intake of vitamin E and lower intake of alcohol. NS was significantly related to higher intake of fish, fat and alcohol and lower consumption of cereals, milk products and carbohydrates. No significant associations between P and intake of foods and nutrients were observed. CONCLUSIONS: Our results suggest that there is an association between temperament traits and diet. Especially greater HA seems to associate with poorer diet quality and greater RD with healthier diet quality.

Telomere Length and Frailty: The Helsinki Birth Cohort Study.

OBJECTIVES: Telomere length is associated with aging-related pathologies. Although the association between telomere length and frailty has been studied previously, only a few studies assessing longitudinal changes in telomere length and frailty exist. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: A subpopulation of the Helsinki Birth Cohort Study consisting of 1078 older adults aged 67 to 79 years born in Helsinki, Finland, between 1934 and 1944. MEASURES: Relative leukocyte telomere length (LTL) was measured using quantitative real-time polymerase chain reaction at the average ages of 61 and 71 years, and at the latter the participants were assessed for frailty according to Fried criteria. RESULTS: The mean ± SD relative LTLs were 1.40 ± 0.29 (average age 61 years) and 0.86 ± 0.30 (average age 71 years) for the cohort. A trend of shorter mean relative LTL across frailty groups was observed at 61 years (P = .016) and at 71 years (P = .057). Relative LTL at age 61 years was significantly associated with frailty: per 1-unit increase in relative LTL, the corresponding relative risk ratio (RRR) of frailty was 0.28 (95% confidence interval [CI] 0.08-0.97), adjusting for several confounders. Also, LTL at age 71 years was associated with frailty (RRR 0.18, 95% CI 0.04-0.81) after adjustment for sex, age, and adult socioeconomic status, but further adjustment attenuated the association. No associations between telomere shortening and frailty were observed during the 10-year follow-up. CONCLUSIONS: Shorter relative LTL was associated with frailty in cross-sectional and longitudinal analyses, but telomere shortening was not, suggesting that short LTL may be a biomarker of frailty.

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants.

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (ß = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; ß = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

Prenatal and childhood growth and physical performance in old age--findings from the Helsinki Birth Cohort Study 1934-1944.

Health in adulthood is in part a consequence of development and growth taking place during sensitive periods in early life. It has not been explored previously whether early growth is associated with physical performance in old age from a life course perspective taking into account health-related behavior, biological risk factors, and early life experiences. At a mean age of 71 years, physical performance was assessed using the Senior Fitness Test (SFT) in 1078 individuals belonging to the Helsinki Birth Cohort Study. We used multiple linear regression analysis to assess the association between the SFT physical fitness scores and individual life course measurements. Several adult characteristics were associated with physical performance including socioeconomic status, lifestyle factors, and adult anthropometry. Higher birth weight and length were associated with better physical performance, even after adjusting for potential confounders (all p values <0.05). The strongest individual association between life course measurements and physical performance in old age was found for adult body fat percentage. However, prenatal growth was independently associated with physical performance seven decades later. These findings suggest that physical performance in old age is at least partly programmed in early life.

Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits.

OBJECTIVE: Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. RESEARCH DESIGN AND METHODS: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. RESULTS: We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (≥9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m(2) higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (≥7 to <9 h). CONCLUSIONS: Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants. Until further mechanistic examination of the nominally significant interactions is conducted, recommendations applicable to the general population regarding diet­specifically higher carbohydrate and lower fat composition­and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants.