A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts.
Ontology highlight
ABSTRACT:
SUBMITTER: Burrows K
PROVIDER: S-EPMC10980110 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts.
Burrows Kimberley K Heiskala Anni A Bradfield Jonathan P JP Balkhiyarova Zhanna Z Ning Lijiao L Boissel Mathilde M Chan Yee-Ming YM Froguel Philippe P Bonnefond Amelie A Hakonarson Hakon H Alves Alessander Couto AC Lawlor Deborah A DA Kaakinen Marika M Järvelin Marjo-Riitta MR Grant Struan F A SFA Tilling Kate K Prokopenko Inga I Sebert Sylvain S Canouil Mickaël M Warrington Nicole M NM
medRxiv : the preprint server for health sciences 20240316
Genetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in genome-wide association studies (GWASs). Using childhood body mass index (BMI) as an example, we included 71,336 participants from six cohorts and estimated the slope and area under th ...[more]
Similar Datasets
Project description:Several studies have found an association between overweight and asthma, yet the temporal relationship between their onsets remains unclear. We investigated the development of body mass index (BMI) from birth to adolescence among 2,818 children with and without asthma from a Swedish birth cohort study, the BAMSE (a Swedish acronym for "children, allergy, milieu, Stockholm, epidemiology") Project, during 1994-2013. Measured weight and height were available at 13 time points throughout childhood. Asthma phenotypes (transient, persistent, and late-onset) were defined by timing of onset and remission. Quantile regression was used to analyze percentiles of BMI, and generalized estimating equations were used to analyze the association between asthma phenotypes and the risk of high BMI. Among females, BMI development differed between children with and without asthma, with the highest BMI being seen among females with persistent asthma. The difference existed throughout childhood but increased with age. For example, females with persistent asthma had 2.33 times' (95% confidence interval: 1.21, 4.49) greater odds of having a BMI above the 85th percentile at age ≥15 years than females without asthma. Among males, no clear associations between asthma and BMI were observed. In this study, persistent asthma was associated with high BMI throughout childhood among females, whereas no consistent association was observed among males.
| S-EPMC5860555 | biostudies-literature
Project description:Metabolic risk varies within adult body mass index (BMI) categories; however, the development of BMI-specific metabolic risk from childhood is unknown.The sample included 895 adults (20-38 years of age; 43% male, 34% black) from the Bogalusa Heart Study (1995-2002), who had been measured as children (5-18 years of age) in 1981-1982. Adult metabolic risk was assessed using two definitions: Cardiometabolic risk factor clustering (RFC) included two or more abnormal risk factors [blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides, and fasting glucose] and insulin resistance (IR), comprising the top quartile of the homeostasis model of insulin resistance (HOMA-IR) distribution. Logistic regression, within BMI categories, was used to predict adult metabolic risk from childhood mean arterial pressure (MAP), HDL-C, low-density lipoprotein cholesterol (LDL-C), glucose, and triglycerides. Covariates included childhood age, race, sex, adult BMI, and length of follow-up.The prevalence of the adult abnormal metabolic risk profile varied by definitions of metabolic risk (normal weight, 5%-9%; overweight, 15%-23%; and obese, 40%-53%). The adult abnormal profile was associated with higher childhood LDL-C [IR, odds ratio (OR), 1.95; 95% confidence interval (CI), 1.06-3.58) and insulin (IR, OR, 1.69; CI, 1.10-2.58) in normal-weight adults; lower childhood HDL-C in overweight adults (RFC, OR, 0.61; CI, 0.40-0.94); and higher childhood MAP (RFC, OR, 1.75; CI, 1.24-2.47) and glucose (IR, OR,1.38; CI, 1.06-1.81) in obese adults.Some childhood metabolic risk factors are moderately associated with adult BMI-specific metabolic risk profiles. The ability to identify children with high future adult cardiovascular risk may initiate early treatment options.
| S-EPMC3035100 | biostudies-other
Project description:ImportanceThe incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity.ObjectivesTo investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight.Design, setting, and participantsThis investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307 677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016.Main outcomes and measuresChildhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (≤55 years) or late (>55 years) age at diagnosis.ResultsThe study cohort comprised 307 677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI z score was positively associated with early ischemic stroke. At age 13 years, a BMI z score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI z scores. Among children with above-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations.Conclusions and relevanceIndependent of birth weight, above-average childhood BMI and increases in BMI during childhood are positively associated with early adult ischemic stroke. To avoid the occurrence of early ischemic stroke associated with childhood overweight and obesity, these results suggest that all children should be helped to attain and maintain healthy weights.
| S-EPMC5710582 | biostudies-literature
Project description:BackgroundMammographic density (MD) is strongly associated with breast cancer risk. We examined whether body mass index (BMI) partially explains racial and ethnic variation in MD.MethodsWe used multivariable Poisson regression to estimate associations between BMI and binary MD [Breast Imaging Reporting and Database System (BI-RADS) A&B versus BI-RADS C&D] among 160,804 women in the Utah mammography cohort. We estimated associations overall and within racial and ethnic subgroups and calculated population attributable risk percents (PAR%).ResultsWe observed the lowest BMI and highest MD among Asian women, the highest BMI among Native Hawaiian and Pacific Islander women, and the lowest MD among American Indian and Alaska Native (AIAN) and Black women. BMI was inversely associated with MD [RRBMI≥30 vs. BMI<25 = 0.43; 95% confidence interval (CI), 0.42-0.44] in the full cohort, and estimates in all racial and ethnic subgroups were consistent with this strong inverse association. For women less than 45 years of age, although there was statistical evidence of heterogeneity in associations between BMI and MD by race and ethnicity (P = 0.009), magnitudes of association were similar across groups. PAR%s for BMI and MD among women less than 45 years were considerably higher in White women (PAR% = 29.2, 95% CI = 28.4-29.9) compared with all other groups with estimates ranging from PAR%Asain = 17.2%; 95% CI, 8.5 to 25.8 to PAR%Hispanic = 21.5%; 95% CI, 19.4 to 23.6. For women ≥55 years, PAR%s for BMI and MD were highest among AIAN women (PAR% = 37.5; 95% CI, 28.1-46.9).ConclusionsWhile we observed substantial differences in the distributions of BMI and MD by race and ethnicity, associations between BMI and MD were generally similar across groups.ImpactDistributions of BMI and MD may be important contributors to breast cancer disparities.
| S-EPMC9250611 | biostudies-literature
Project description:Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.
| S-EPMC8531156 | biostudies-literature
Project description:Background: Many states have adopted school-based BMI screening or surveillance programs in an effort to address high rates of childhood obesity, some of which involve provision of confidential BMI reports to parents. While there is evidence that parents are attuned to information in the reports, there is less evidence showing that the reports are effective in preventing excess childhood weight gain. Methods: Data from Arkansas, the state with the nation's first and longest running and BMI screening program, were used to measure the impact of BMI reports. This was done through a regression discontinuity design that compared future BMI z-scores among children falling within a narrow band around the obese and overweight thresholds. We derived the effects of BMI reports by comparing students who received different types of reports around the relevant threshold. Results: While we are unable to detect any differences in BMI z-scores between the children who received the overweight report and the children who received the healthy weight report, we detected some differences between children who received the obese report and children who received the overweight report. These findings hold across subsamples by age, minority status, and school meal status. Conclusions: Based on these data, overweight or obese reports to do not meaningfully impact future BMI z-scores. This may be due, in part, to the format of parental reports, which may dampen the surprise element of an overweight or obese report.
| S-EPMC9529310 | biostudies-literature
Project description:Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.
| S-EPMC5132154 | biostudies-literature
Project description:BackgroundThe relationship between obesity and asthma is an area of debate.ObjectiveTo investigate the association of elevated body mass index (BMI) at a young age and young adult asthma.MethodsBMI, questionnaires, and serologic tests results were analyzed in participants of a predominantly white, middle-class, population-based birth cohort from Detroit, Michigan at 6 to 8 and 18 years of age. Asthma diagnosis was based on medical record data. Allergen specific IgE was analyzed using UniCAP, with atopy defined as 1 or more allergen specific IgE levels of 0.35 kU/L or higher. Overweight was defined as a BMI in 85th percentile or higher.ResultsA total of 10.6% of overweight males at 6 to 8 years of age had current asthma at 18 to 20 years of age compared with 3.2% of males who were normal or underweight (relative risk [RR], 3.3; 95% confidence interval [CI], 1.0-11.0; P=.048). A total of 19.6% of females who were overweight at 6 to 8 years of age had asthma compared with 10.3% of females who were normal or underweight (RR, 1.9; 95% CI, 0.9-3.9; P=.09). After adjustment for atopy at 6 to 8 years of age, overweight males had an adjusted RR of 4.7 (95% CI, 1.4-16.2; P=.01), and overweight females had an adjusted RR of 1.7 (95% CI, 0.8-3.3; P=.15). Change in BMI between 6 to 8 years of age and 18 to 20 years of age was also examined. Patients with persistently elevated BMI exhibited increased risk of asthma as young adults (RR, 2.4; 95% CI, 1.2-4.7) but not with an increasing BMI (RR, 0.8; 95% CI, 0.3-2.2) or a decreasing BMI (RR, 0.8; 95% CI, 0.3-2.2).ConclusionOverweight males 6 to 8 years of age have increased risk of asthma as young adults. Being overweight remains a predictor of asthma after adjustment for early atopy. A similar but not statistically significant trend was also seen among overweight females. Overweight body habitus throughout childhood is a risk factor for young adult asthma.
| S-EPMC3769639 | biostudies-literature
Project description:BackgroundExcess weight in adulthood is one of the few modifiable risk factors for pancreatic cancer, and height has associations as well. This leads to question whether body weight and height in childhood are associated with adult pancreatic cancer.ObjectiveTo examine if childhood body mass index (BMI; kg/m2) and height are associated with pancreatic cancer in adult life.MethodsWe linked 293,208 children born from 1930-1982 in the Copenhagen School Health Records Register who had measured values of weights and heights at ages 7-13 years with the Danish Cancer Registry to identify incident pancreatic cancer cases from 1968-2012. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regressions.ResultsDuring 8,207,015 person-years of follow-up, 1,268 pancreatic cancer cases were diagnosed. Childhood BMI z-scores at ages 7-13 years were positively and significantly associated with pancreatic cancer in men and women up to age 70 years; beyond age 70 the associations diminished. The HRs of pancreatic cancer were 1.13 (95% CI: 1.05-1.21) and 1.18 (95% CI: 1.09-1.27) per BMI z-score at ages 7 and 13 years, respectively. A BMI ≥1.5 z-score at ages 7, 10 and 13 years was positively and significantly associated with pancreatic cancer; however, the effect did not differ from having a BMI z-score ≥1.5 at only one of these ages. Positive, albeit non-statistically significant, associations were identified with height.ConclusionsBMI at all ages from 7-13 years is positively and linearly associated with adult pancreatic cancer; the higher the BMI, the higher the risk. Excess childhood BMI may be indicative of processes initiated early in life that lead to this cancer. Prevention of childhood adiposity may decrease the burden of pancreatic cancer in adults.
| S-EPMC5788457 | biostudies-literature
Project description:BackgroundAlthough associations between cumulative risk, sleep, and overweight/obesity have been demonstrated, few studies have examined relationships between these constructs longitudinally across childhood. This study investigated how cumulative risk and sleep duration are related to current and later child overweight/obesity in families across the United States sampled for high sociodemographic risk.MethodsWe conducted secondary analyses on 3690 families with recorded child height and weight within the Fragile Families and Child Well-Being Study. A cumulative risk composite (using nine variables indicating household/environmental, family, and sociodemographic risk) was calculated for each participant from ages 3-9 years. Path analyses were used to investigate associations between cumulative risk, parent-reported child sleep duration, and z-scored child body mass index (BMI) percentile at ages 3 through 9.ResultsHigher cumulative risk experienced at age 5 was associated with shorter sleep duration at year 9, b = - 0.35, p = .01, 95% CI [- 0.57, - 0.11]. At 5 years, longer sleep duration was associated with lower BMI, b = - 0.03, p = .03, 95% CI [- 0.06, - 0.01]. Higher cumulative risk at 9 years, b = - 0.34, p = .02, 95% CI [- 0.57, - 0.10], was concurrently associated with shorter sleep duration. Findings additionally differed by child sex, such that only male children showed an association between sleep duration and BMI.ConclusionsResults partially supported hypothesized associations between child sleep duration, cumulative risk, and BMI emerging across childhood within a large, primarily low socioeconomic status sample. Findings suggest that reducing cumulative risk for families experiencing low income may support longer child sleep duration. Additionally, child sleep duration and BMI are concurrently related in early childhood for male children.
| S-EPMC9447344 | biostudies-literature