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Purpose of Review To examine the evidence that the dietary quality of children changed between the period preceding the COVID-19 pandemic and the first year during the pandemic. Recent Findings A systematic review of the evidence for dietary changes occurring as a result of the pandemic-related restrictions, in Part I of this article, yielded 38 original research articles. These articles had conflicting results, some describing improvements in overall quality and some describing deteriorations. As a whole the studies were characterized by a low study quality, and children were poorly represented. Taken together, these studies do not provide enough evidence to draw conclusions about whether dietary habits changed or not as a result of the pandemic. However, in a wider, narrative review of the psychosocial changes occurring as a result of the COVID-19 pandemic, and the known associations of these factors with a dietary intake in Part II, we conclude that there is a reason to expect that the dietary quality of children might have been adversely affected by the COVID-19 pandemic. Summary One the one hand, the literature fails to provide conclusive evidence on changes in the dietary quality of children resulting from the COVID-19 pandemic. On the other hand, the broader literature supports the hypothesis that children’s dietary quality will have declined during the pandemic. Taken together, we urgently need more high-quality research on children’s changes in dietary intake occurring over the pandemic. This will provide important information on whether any potential long-term consequences of such changes, if they exist, need to be examined and ameliorated.

Background Early childhood (0–3 years) is a critical period for obesity prevention, when tendencies in eating behaviors and physical activity are established. Yet, little is understood about how the environment shapes children's genetic predisposition for these behaviors during this time. The Baylor Infant Twin Study (BITS) is a two phase study, initiated to study obesity risk factors from infancy. Data collection has been completed for Phase 1 in which three sub‐studies pilot central measures for Phase 2. A novel infant temperament assessment, based on observations made by trained researchers was piloted in Behavior Observation Pilot Protocol (BOPP) study, a new device for measuring infant feeding parameters (the “orometer”) in the Baylor Infant Orometer (BIO), and methods for analyzing DNA methylation in twins of unknown chorionicity in EpiTwin. Methods EpiTwin was a cross‐sectional study of neonatal twins, while up to three study visits occurred for the other studies, at 4‐ (BOPP, BIO), 6‐ (BOPP), and 12‐ (BOPP, BIO) of age. Measurements for BOPP and BIO included temperament observations, feeding observations, and body composition assessments while EpiTwin focused on collecting samples of hair, urine, nails, and blood for quantifying methylation levels at 10 metastable epialleles. Additional data collected include demographic information, zygosity, chorionicity, and questionnaire‐based measures of infant behaviors. Results Recruitment for all three studies was completed in early 2020. EpiTwin recruited 80 twin pairs (50% monochorionic), 31 twin pairs completed the BOPP protocol, and 68 singleton infants participated in BIO. Conclusions The psychometric properties of the data from all three studies are being analyzed currently. The resulting findings will inform the development of the full BITS protocol, with the goal of completing assessments at 4‐, 6‐, 12‐, and 14‐month of age for 400 twin pairs.

Aim To investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D). Materials and methods The Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline. Results After screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance. Conclusions The longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D.

Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D., Fumiaki Imamura and colleagues investigate the association between concentrations of fatty acid involved in de-novo lipogensis and incidence of Type 2 diabetes., Author summary Why was this study done? De novo lipogenesis (DNL) is a metabolic pathway involved in the endogenous synthesis of specific fatty acids, such as 16:0, 16:1n7, 18:0, and 18:1n9, and it is linked to the pathophysiology of cardiometabolic diseases, including type 2 diabetes (T2D). Circulating or tissue concentrations of these fatty acids have been investigated for the associations with T2D incidence in epidemiological research. However, published studies reported inconsistent associations inconsistently and were subject to publication bias. Summary evidence is not available to date for the associations between these fatty acids and T2D incidence. An integration of available cohort studies would increase statistical power and allow assessment of generalizability, standardization of analytical strategies, and evidence synthesis with the potential publication bias minimized. What did the researchers do and find? As a part of the Fatty Acids and Outcomes Research Consortium (FORCE), we conducted new individual-participant data analyses of 17 cohort studies of a total of 65,225 adults free of T2D at baseline, among whom 15,383 developed incident T2D over up to 20 years of follow-up. The cohort studies analyzed the associations between fatty acids (16:0, 16:1n7, 18:0, and 18:1n9) and the risk of developing T2D with standardized analytic strategy. In pooled analyses, each of the fatty acids was positively associated with a higher risk of developing T2D. The associations were independent of major risk factors for T2D, such as age, sex, race/ethnicity, socioeconomic characteristics, smoking status, physical activity, and obesity. What do these findings mean? The findings provide the first summary evidence to date for the positive relationships of concentrations of the DNL-related fatty acids with a risk of T2D, indicating the strong relevance of DNL and its determinants to the development of T2D. These fatty acids potentially reflect the status of DNL activity, which may be stimulated or suppressed by a combination of carbohydrate intake, alcohol intake, polyunsaturated fatty acid intake, and other lifestyle and clinical factors. Therefore, the current findings indicate the need for investigation into determinants and consequences of elevated concentrations of these fatty acids. Despite several advantages of our individual-level data analysis in this pooling project, the results cannot establish whether elevated concentrations of these fatty acids caused the development of T2D or whether underlying peripheral or hepatic insulin resistance, for example, may elevate both the fatty acid concentrations and the risk of T2D independently.

Although hyperlipidemia is traditionally considered a risk factor for type 2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL cholesterol (LDL-C) increases T2D risk. We thus sought to more comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that levels of circulating LDL-C were negatively associated with T2D prevalence (odds ratio 0.41 [95% CI 0.39, 0.43] per mmol/L unit of LDL-C), despite positive associations of circulating LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower circulating LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n = 431,167) and the Global Lipids Genetics Consortium (n = 188,577), and data on T2D from the Diabetes Genetics Replication and Meta-Analysis consortium (n = 898,130). We identified 31 loci associated with lower circulating LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this dual phenotype, and nine have previously been implicated in nonalcoholic fatty liver disease. These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C–lowering medications.

BackgroundVitamin D inadequacy affects almost 50% of adults in the United States and is associated with numerous adverse health effects. Vitamin D concentration [25(OH)D] is a complex trait with genetic and environmental predictors that work in tandem to influence 25(OH)D and may determine how much vitamin D intake is required to reach an optimal 25(OH)D concentration. To date, there has been little investigation into how genetics and environment interact to affect 25(OH)D.ObjectiveInteractions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultra-violet (UV) radiation (PGS*UV) were evaluated separately in individuals of African or European ancestry.MethodsMega-analyses were performed using three independent cohorts (N=9,668; African ancestry n=1,099; European ancestry n=8,569). Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (DF) and 2-DF models, respectively. All models controlled for age, sex, body mass index (BMI), cohort, and dietary intake/available UV. Additionally, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level of genetic risk of 25(OH)D deficiency.ResultsThe 2-DF PGS*intake, 1-DF PGS*UV and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p=3.3×10−18, 2.1×10−2, and 2.4×10−19, respectively), but not in those of African ancestry. In European-ancestry participants who reached IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D (>20ng/ml) increased as genetic risk decreased (72% vs 89% in the highest vs lowest risk categories; p=0.018).ConclusionsAvailable UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk of deficiency may require more vitamin D exposure to maintain optimal 25(OH)D concentrations. Overall, the results showcase the importance of incorporating both environmental and genetic factors into analyses, as well as the potential for gene-environment interactions to inform personalized dosing of vitamin D.Sources of SupportARICThe Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The authors thank the staff and participants of the ARIC study for their important contributions.Funding for GENEVA was provided by National Human Genome Research Institute grant U01HG004402 (E. Boerwinkle).MESAMESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491.The MESA CARe data used for the analyses described in this manuscript were obtained through Genetics (accession numbers). Funding for CARe genotyping was provided by NHLBI Contract N01-HC-65226.Funding support for the Vitamin D dataset was provided by grant HL096875WHIThe WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This manuscript was not prepared in collaboration with investigators of the WHI, has not been reviewed and/or approved by the Women’s Health Initiative (WHI), and does not necessarily reflect the opinions of the WHI investigators or the NHLBI.WHI PAGE is funded through the NHGRI Population Architecture Using Genomics and Epidemiology (PAGE) network (Grant Number U01 HG004790). Assistance with phenotype harmonization, SNP selection, data cleaning, meta-analyses, data management and dissemination, and general study coordination, was provided by the PAGE Coordinating Center (U01HG004801-01).Funding support for WHI GARNET was provided through the NHGRI Genomics and Randomized Trials Network (GARNET) (Grant Number U01 HG005152). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004424). The datasets used for the analyses described in this manuscript were obtained from dbGaP athttp://www.ncbi.nlm.nih.gov/sites/entrez?db=gapthrough dbGa Paccession phs000200.v11.p3.Funding for WHI SHARe genotyping was provided by NHLBI Contract N02-HL-64278.OtherKEH was supported by an NLM training grant to the Computation and Informatics in Biology and Medicine Training Program (NLM 5T15LM007359). Computational resources were supported by a core grant to the Center for Demography and Ecology at the University of Wisconsin-Madison (P2C HD047873).JM was supported by the Department of Ophthalmology and Visual Sciences, and by an unrestricted grant to the Department of Ophthalmology and Visual Sciences from the Research to Prevent Blindness, and by National Institutes of Health, National Eye Institute grants R01 EY016686, R01 EY025292.

Introduction In observational studies, the association between the Dietary Approaches to Stop Hypertension (DASH) diet and incident heart failure has been inconsistent. It was hypothesized that higher DASH diet concordance has a protective effect on heart failure in a multi-ethnic cohort. Methods The Multi-Ethnic Study of Atherosclerosis cohort includes men and women of multiple ethnicities who were aged 45–84 years and free of clinical cardiovascular disease at baseline. Participants were recruited between 2000 and 2002 from six U.S. communities and followed for incident cardiovascular health events through 2015 for the purpose of this data set. Diet was measured using food-frequency questionnaires. Cox proportional hazards analysis was used to investigate the associations of the DASH diet concordance with incident heart failure in 2017–2018. Results During a median 13 years of follow-up, 179 of 4,478 participants developed heart failure, corresponding to a rate of 3.4 per 1,000 person years. Heart failure incidence rates did not vary significantly by DASH quintile for the population as a whole. In participants younger than 75 years, highest DASH concordance was associated with a lower risk of incident heart failure compared with those in the lowest quintile (hazard ratio=0.4, 95% CI=0.2, 0.9 vs all participants hazard ratio=1.0, 95% CI=0.2, 0.9) after adjusting for demographics, energy consumption, and known cardiovascular confounders. Conclusions This study supports the hypothesis that DASH is beneficial in heart failure prevention within the individuals aged less than 75 years subgroup, an idea that to date was substantiated only by much smaller studies or in less diverse patient populations.

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk., Yang et al. examine whether genetic ancestry is associated with genetic variation in fatty acid desaturases and plasma phospholipid levels of long chain polyunsaturated fatty acids (LC-PUFAs) in Hispanic Americans. They find strong associations between Amerind genetic ancestry and LC-PUFA levels; and report that the well-known FADS rs174537 variant was associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides.

Supplemental Digital Content is available in the text., Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake. Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele; P

OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance–weighted meta-analysis. RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSIONS Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p, Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P −3 ). Hypermethylation of cg18181703 ( SOCS3 ) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality ( P =5.7×10 −15 ). Ten additional diet-associated CpGs were nominally associated with all-cause mortality ( P P −4 ). For example, hypermethylation of cg11250194 ( FADS2 ) was associated with lower triglyceride concentrations (MR, P =1.5×10 −14 ).and hypermethylation of cg02079413 ( SNORA54 ; NAP1L4 ) was associated with body mass index (corrected MR, P =1×10 −6 ). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

Background and Purpose— Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort. Methods— The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models. Results— Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07–2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function. Conclusions— The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.

A substantial body of research suggests that efforts to prevent pediatric obesity may benefit from targeting not just what a child eats, but how they eat. Specifically, child obesity prevention should include a component that addresses reasons why children have differing abilities to start and stop eating in response to internal cues of hunger and satiety, a construct known as eating self‐regulation . This review summarizes current knowledge regarding how caregivers can be an important influence on children's eating self‐regulation during early childhood. First, we discuss the evidence supporting an association between caregiver feeding and child eating self‐regulation. Second, we discuss what implications the current evidence has for actions caregivers may be able to take to support children's eating self‐regulation. Finally, we consider the broader social, economic, and cultural context around the feeding environment relationship and how this intersects with the implementation of any actions. As far as we are aware, this is the first American Heart Association (AHA) scientific statement to focus on a psychobehavioral approach to reducing obesity risk in young children. It is anticipated that the timely information provided in this review can be used not only by caregivers within the immediate and extended family but also by a broad range of community‐based care providers.

Background Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain. Methods We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk. Results We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR. Conclusions We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age.

Background: Several recent studies have linked higher blood levels of the long-chain omega-3 polyunsaturated fatty acids (PUFAs) with lower risk of certain disease outcomes, in particular cardiovascular disease (CVD). Limited studies have evaluated associations between n-3 PUFA levels and total and cause-specific mortality. Methods: We meta-analyzed the association of circulating omega-3 PUFAs with total and cause-specific mortality from 15 distinct cohorts in 10 countries following a total of 36,840 individuals (baseline average age 66 yrs; 47% female; median follow-up 13.7 yrs), with 11,635 deaths. Total mortality, and 3 cause-specific mortalities (CVD, cancer or other), were separately predicted by levels of the long chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) and the Omega-3 index (EPA+DHA), as well as levels of alpha-linolenic acid (ALA, an intermediate chain n-3 PUFA). Using cohort-specific fatty acid levels (range from 10 th to 90 th percentiles), each cohort fit a Cox regression model adjusting for demographics, health related covariates, and n-6 PUFA levels. Cohort-specific estimates were pooled with inverse-variance weighted meta-analysis. Results: Higher levels of EPA, DPA, DHA and the Omega-3 index were all associated with lower all-cause mortality [EPA meta-analysis Hazard Ratio (HR)=0.90 (95% CI: 0.85, 0.95), DPA HR=0.84 (95% CI: 0.77, 0.91), DHA HR=0.84 (95% CI: 0.75, 0.93), Omega-3 index HR = 0.84 (95% CI 0.77, 0.92) (Figure)], as well as for each cause-specific mortality (CVD, cancer and other; HRs from 0.85 to 0.92). ALA showed no association with total-mortality or cause-specific mortality [HRs from 0.97 to 1.00)]. Conclusions: We have found strong evidence of inverse associations between long-chain omega-3 PUFA levels and all-cause and cause-specific mortality. Further controlled studies are needed in order to determine the extent to which these observations represent a causal or coincidental relationships.

PURPOSE OF REVIEW: Current feeding advice to prevent pediatric obesity focusses on caregiver feeding behaviors. This review integrates newer data showing that child appetitive traits also have a genetic component. RECENT FINDINGS: Caregiver feeding behaviors robustly correlate with child eating behaviors; however there is also a strong heritable component. SUMMARY: The satiety cascade delineates the biological drive underlying hunger, satiation and satiety. Innate individual differences exist for the components of the satiety cascade, which may explain the heritability of child eating behaviors. However, given the correlation of caregiver feeding behaviors with child eating behaviors any etiological model should include both genetic/biological components and environmental. Integrating the biological etiology of child eating behaviors into the current environmental model has implications for tailoring feeding advice which needs to move from a “one size fits all” approach, to one that is tailored to individual differences in children’s biological drives to appetite.

Although hyperlipidemia is traditionally considered a risk factor for type-2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL-C increases T2D risk. We thus sought to comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that LDL-C was negatively associated with T2D (OR=0.43[0.41, 0.45] per mmol/L unit of LDL-C), despite positive associations of LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n=431,167) and the GLGC consortium (n=188,577), and T2D from the DIAGRAM consortium (n=898,130). We identified 31 loci associated with lower LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this phenotype, and 9 have previously been implicated in non-alcoholic fatty liver disease. Finally, two-sample Mendelian randomization analyses suggest that low LDL-C causes T2D, although causal interpretations are challenging due to pleiotropy. Our findings extend our current understanding of the higher T2D risk among individuals with low LDL-C, and of the underlying mechanisms, including those underlying the diabetogenic effect of LDL-C-lowering medications.

Background DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific. Results For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues. Conclusions In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease. Electronic supplementary material The online version of this article (10.1186/s13059-019-1708-1) contains supplementary material, which is available to authorized users.

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88–0.99), 0.78 (0.70–0.85), and 0.88 (0.79–0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88–1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86–0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. Conclusions: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

ContextVitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D levels has been discovered.ObjectiveTherefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of morbidity and mortality from deficient 25(OH)D.DesignUsing PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors.Patients or Other ParticipantsParticipants (European ancestry n=9,569, African ancestry n=2,761) came from three cohort studies.Main Outcome Measure(s)Blood concentrations of 25(OH)D.ResultsThe PGS for African ancestry was derived using all input SNPs (a p-value cut-off of 1.0) and had an R2of 0.3%; for European ancestry, the optimal PGS used a p-value cut-off of 3.5×10−4in the target/tuning dataset and had an R2of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/ml lower than those with lowest genetic risk (p=0.0463 to 3.2×10−13), requiring an additional 467 to 500 IU of vitamin D intake to maintain equivalent 25(OH)D.ConclusionsPGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.

International audience; BACKGROUND:Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.OBJECTIVE:We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.METHODS:Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants.RESULTS:There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides.CONCLUSIONS:Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions of these traits to early dysglycemia (prediabetes or newly diagnosed diabetes). In separate models, reduced insulin sensitivity, reduced disposition index, and reduced insulin clearance were associated with dysglycemia. In a joint model, only insulin resistance and reduced insulin secretion were associated with dysglycemia. Models with insulin sensitivity, disposition index, or three insulin traits had the highest discriminative value for dysglycemia (area under the receiver operating characteristics curve of 0.82 to 0.89). These results suggest that in the race groups studied, insulin resistance and compromised insulin secretion are the main independent underlying defects leading to early dysglycemia.

Objectives To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs). Methods Data were included from 70,750 NHW and NHB postmenopausal women from the Women’s Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline. Results In both crude and adjusted models, NHBs were more likely to experience ≥10% weight gain than NHWs within the same category of baseline weight status. Moreover, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain in both crude and adjusted models. Age-stratified results were consistent with overall findings. In all age categories, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain. Based on the results of adjusted models, the joint influence of NHB race/ethnicity and weight status on risk of postmenopausal weight gain was both sub-additive and sub-multiplicative. Conclusion NHBs are more likely to experience postmenopausal weight gain than NHWs, and the disparity in risk is most pronounced among those who are normal weight at baseline. To address the disparity in postmenopausal obesity, future studies should focus on identifying and modifying factors that promote weight gain among normal weight NHBs.

INTRODUCTION: In 2010, the American Heart Association initiated Life’s Simple 7 with the goal of significantly improving cardiovascular health by the year 2020. The association of Life’s Simple 7 with risk of peripheral artery disease has not been thoroughly explored. METHODS: Racially diverse individuals from the Multi-Ethnic Study of Atherosclerosis (2000–2012) were followed for incident peripheral artery disease (ankle brachial index ≤0.90) and decline in ankle brachial index (≥0.15) over approximately 10 years of follow-up. Cox and logistic regression were used to assess associations of individual Life’s Simple 7 components (score 0–2) and overall Life’s Simple 7 score (score 0–14) with incident peripheral artery disease and ankle brachial index decline, respectively, adjusted for age, sex, race/ethnicity, education, and income. Analyses were performed in 2016–2018. RESULTS: Of 5,529 participants, 251 (4.5%) developed incident peripheral artery disease; 419 (9.8%) of 4,267 participants experienced a decline in ankle brachial index. Each point higher for the overall Life’s Simple 7 score was associated with a 17% lower rate of incident peripheral artery disease (hazard ratio=0.83, 95% CI=0.78, 0.88, p

H.G. was funded by the NIHR Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre. I.K. was supported by the EU PhenoMeNal project (Horizon 2020, grant no. 654241) and the UK Dementia Research Institute, which is supported by the MRC, the Alzheimer’s Society and Alzheimer’s Research UK. S. Thériault was supported by the Canadian Institutes of Health Research and Université Laval (Quebec City, Canada). L.R. was supported by Forschungs- und Förder-Stiftung INOVA, Vaduz, Liechtenstein. D.C. holds a McMaster University Department of Medicine Mid-Career Research Award. M.B. is supported by NIH grant R01-DK062370. P.v.d.H. was supported by ICIN-NHI and Marie Skłodowska-Curie GF (call: H2020-MSCA-IF-2014; Project ID: 661395). C.H. was supported by a core MRC grant to the MRCHGU QTL in Health and Disease research programme. N.V. was supported by Marie Skłodowska-Curie GF (grant no. 661395) and ICIN-NHI. Q.L. is partially supported by the National Natural Sciences Foundation of China (No. 81873909), Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01) and ZJLab. P.E. acknowledges support from the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London, the NIHR Health Protection Research Unit in Health Impact of Environmental Hazards (HPRU-2012-10141), the Medical Research Council (MRC) and Public Health England (PHE) Centre for Environment and Health (MR/L01341X/1) and Health Data Research (HDR) UK. P.E. is supported by a UK Dementia Research Institute (DRI) professorship, UK DRI at Imperial College London, funded by the MRC, Alzheimer’s Society and Alzheimer’s Research UK. This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology; LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders; grant no. 695313), ERANID (Understanding the interplay between cultural, biological and subjective factors in drug use pathways; PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics; MR/N027558/1), the FP7 projects IMAGEMEND (grant no. 602450; IMAging GEnetics for MENtal Disorders) and MATRICS (grant no. 603016), the Innovative Medicine Initiative Project EU-AIMS (grant. no115300-2), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions; MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; and Forschungsnetz AERIAL 01EE1406A and 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2 and SFB 940/2), the Medical Research Foundation and Medical Research Council (MR/R00465X/1), the Human Brain Project (HBP SGA 2). Further support was provided by grants from ANR (project AF12-NEUR0008-01-WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1); and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence.

PURPOSE OF REVIEW: This narrative review describes the evidence for both genetic and environmental influences on child appetitive traits, and suggests ways of thinking about how these interact and correlate to influence how a child eats. RECENT FINDINGS: Emerging evidence from social network analysis, and from longitudinal studies questioning the direction of association between parent feeding behaviors and child obesity risk, suggest that children’s genes may shape the environmental risk for obesity that they are exposed to. SUMMARY: There is strong evidence that child appetitive traits are both heritable, and shaped by the environment. Instead of thinking about how genetic and environmental factors operate independently on each appetitive trait, research needs to expand the current paradigm to examine how genes and environments interact and shape each other.

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. We conducted a genome-wide association study (GWAS) of alcohol use in ~480,000 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 novel, common loci, and investigated their potential functional significance using magnetic resonance imaging data, gene expression and behavioral studies in Drosophila. Our results identify new genetic pathways associated with alcohol consumption and suggest common genetic mechanisms with several neuropsychiatric disorders including schizophrenia.

RATIONALE: Although short sleep duration has been linked to unhealthy dietary patterns, little is known about the association of obstructive sleep apnea (OSA), a disorder characterized by sleep fragmentation and diet. STUDY OBJECTIVES: Investigate associations between diet quality and OSA in the Multi-Ethnic Study of Atherosclerosis and assess whether reductions in slow-wave sleep (stage N3) and rapid eye movement (REM) sleep are potential mediators for these associations. METHODS: A diverse population (N = 1813) completed a food frequency questionnaire and underwent Type 2 in-home polysomnography, which included measurement of N3 and REM sleep and apnea–hypopnea index (AHI). Moderate-to-more severe OSA was defined as having an AHI > 15 events/hr. RESULTS: Participants were 53.9% female with a mean age of 68.3 (SD 9.1) years. Approximately 33.8% were categorized as having moderate-to-more severe OSA. In adjusted analyses, OSA was associated with lower intakes of whole grains, (β = −0.200, SE = 0.072, p < 0.01), higher intakes of red/processed meat, (β = −0.440, SE = 0.136, p < 0.01), and lower overall diet quality (β = −1.286, SE = 0.535, p = 0.02). Stage N3 sleep partially explained the associations between red/processed meat and overall diet quality score with OSA. CONCLUSIONS: Moderate-to-more severe OSA is associated with a less healthy dietary profile that is partially explained by reduced N3 sleep. These findings suggest the opportunity to target sleep quality in interventions aimed at improving cardio-metabolic risk factors in patients with OSA.

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2&nbsp

Sleep duration and sleep quality are important predictors of risk for cardiovascular disease (CVD). One potential link between sleep health and CVD is through lifestyle factors such as diet. To clarify the association between diet and sleep, we assessed the associations of sleep duration and insomnia symptoms with current Mediterranean-style diet (aMed) and with historical changes in aMed score. Actigraphy-measured sleep duration and self-reported insomnia symptoms categorized as insomnia with short sleep (

BackgroundTwin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.MethodMultivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).ResultsSignificant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.ConclusionsThe aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Previous studies have documented the primarily genetic aetiology for the stronger phenotypic covariance between reading disability and ADHD inattention symptoms, compared to hyperactivity-impulsivity symptoms. In this study, we examined to what extent this covariation could be attributed to "generalist genes" shared with general cognitive ability or to "specialist" genes which may specifically underlie processes linking inattention symptoms and reading difficulties. We used multivariate structural equation modeling on IQ, parent and teacher ADHD ratings and parent ratings on reading difficulties from a general population sample of 1312 twins aged 7.9-10.9 years. The covariance between reading difficulties and ADHD inattention symptoms was largely driven by genetic (45%) and child-specific environment (21%) factors not shared with IQ and hyperactivity-impulsivity; only 11% of the covariance was due to genetic effects common with IQ. Aetiological influences shared among all phenotypes explained 47% of the variance in reading difficulties. The current study, using a general population sample, extends previous findings by showing, first, that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genes contributing to general cognitive ability and, second, that child-specific environment factors, independent from IQ, also contribute to the covariation between reading difficulties and inattention symptoms.

Previous research suggests an association between hyperactivity-impulsivity – one of the two behavioural dimensions that form attention deficit hyperactivity disorder – and the temperament characteristic of novelty seeking. We aimed to examine etiological links underlying the co-occurrence between these behaviours using a general population sample of 668 twin pairs, ages 7-10, for whom we obtained parent ratings in middle childhood; and pilot longitudinal data on 76 children. Structural equation modelling confirmed a shared genetic etiology (genetic correlation, rD=.81; 95% confidence intervals [CI]= .34-1.00) and showed that much (64%) of the covariation can be accounted for by shared genetic effects. In addition, causal paths were modelled between the two behaviours; 12% of the variance in novelty seeking at age 7 was accounted for by hyperactive-impulsive behaviors at the same age. The causal effects model fits with the current characterization of hyperactive-impulsive behaviors reflecting a heightened need for stimulation. This has important implications for the management of hyperactive-impulsive behaviors in clinical settings.

Background Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified groups (N = 251), ~75% of individuals met Adult Treatment Panel III criteria for the metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm); however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group 2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed significantly more insulin resistance (IR), and accompanying higher waist circumference and fasting glucose and triglycerides (all P < .01). Since lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined whether these two patterns of lipoprotein diameter were associated with differences across two lipoprotein lipase (LPL) gene variants: D9N (rs1801177) and S447X (rs328). Findings Mixed linear models that controlled for age, sex, center of data collection, and family pedigree revealed no differences between the two groups for the D9N polymorphism (P = .36). However, group 2 contained significantly more carriers (25%) of the 447X variant than group 1 (14%; P = .04). Conclusions This was the first study this kind to show an association between LPL and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern.

Contains fulltext : 89304.pdf (Publisher’s version ) (Open Access) CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. OBJECTIVES: To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. DESIGN: An ADHD and control sibling-pair design. SETTING: Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. PARTICIPANTS: A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. MAIN OUTCOME MEASURES: Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. RESULTS: The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. CONCLUSIONS: The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions. 01 november 2010