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Marie-Jo Brion

Bio: Marie-Jo Brion is an academic researcher from University of Queensland. The author has contributed to research in topics: Offspring & Pregnancy. The author has an hindex of 20, co-authored 34 publications receiving 2906 citations. Previous affiliations of Marie-Jo Brion include Murdoch University & Garvan Institute of Medical Research.

Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that power for 2SLS MR can be derived using the non-centrality parameter (NCP) of the statistical test that is employed to test whether the two-stage least squares regression coefficient is zero and represented theoretically using this NCP-based approach.
Abstract: In Mendelian randomization (MR) studies, where genetic variants are used as proxy measures for an exposure trait of interest, obtaining adequate statistical power is frequently a concern due to the small amount of variation in a phenotypic trait that is typically explained by genetic variants. A range of power estimates based on simulations and specific parameters for two-stage least squares (2SLS) MR analyses based on continuous variables has previously been published. However there are presently no specific equations or software tools one can implement for calculating power of a given MR study. Using asymptotic theory, we show that in the case of continuous variables and a single instrument, for example a single-nucleotide polymorphism (SNP) or multiple SNP predictor, statistical power for a fixed sample size is a function of two parameters: the proportion of variation in the exposure variable explained by the genetic predictor and the true causal association between the exposure and outcome variable. We demonstrate that power for 2SLS MR can be derived using the non-centrality parameter (NCP) of the statistical test that is employed to test whether the 2SLS regression coefficient is zero. We show that the previously published power estimates from simulations can be represented theoretically using this NCP-based approach, with similar estimates observed when the simulation-based estimates are compared with our NCP-based approach. General equations for calculating statistical power for 2SLS MR using the NCP are provided in this note, and we implement the calculations in a web-based application.

859 citations

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TL;DR: Calypso is an easy‐to‐use online software suite that allows non‐expert users to mine, interpret and compare taxonomic information from metagenomic or 16S rDNA datasets and has a focus on multivariate statistical approaches that can identify complex environment‐microbiome associations.
Abstract: Calypso is an easy-to-use online software suite that allows non-expert users to mine, interpret and compare taxonomic information from metagenomic or 16S rDNA datasets. Calypso has a focus on multivariate statistical approaches that can identify complex environment-microbiome associations. The software enables quantitative visualizations, statistical testing, multivariate analysis, supervised learning, factor analysis, multivariable regression, network analysis and diversity estimates. Comprehensive help pages, tutorials and videos are provided via a wiki page.

518 citations

Journal ArticleDOI
TL;DR: Greater maternal prepregnancy weight and gestational weight gain up to 36 weeks of gestation are associated with greater offspring adiposity and adverse cardiovascular risk factors.
Abstract: Background— We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight with offspring adiposity and cardiovascular risk factors. Methods and Results— Data from 5154 (for adiposity and blood pressure) and 3457 (for blood assays) mother-offspring pairs from a UK prospective pregnancy cohort were used. Random-effects multilevel models were used to assess incremental GWG (median and range of repeat weight measures per woman: 10 [1, 17]). Women who exceeded the 2009 Institute of Medicine–recommended GWG were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, C-reactive protein, and interleukin-6 levels and lower high-density lipoprotein cholesterol and apolipoprotein A1 levels. Children of women who gained less than the recommended amounts had lower levels of adiposity, but other cardiovascular risk factors tended to be similar in this group to those of offspring of women gaining recommended amounts. When examined in ...

459 citations

Journal ArticleDOI
TL;DR: While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding, breastfeeding may have causal effects on IQ.
Abstract: BACKGROUND: A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low- or middle-income countries (LMIC) where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP) body mass index (BMI) and intelligence quotient (IQ). METHODS: Standardized approaches for assessing the confounding structure of breastfeeding by socio-economic position were applied to the British Avon Longitudinal Study of Parents and Children (ALSPAC) (N approximately 5000) and Brazilian Pelotas 1993 cohorts (N approximately 1000). This was used to improve causal inference regarding associations of breastfeeding with child BP BMI and IQ. Analyses were extended to include results from a meta-analysis of five LMICs (N approximately 10 000) and compared with a randomized trial of breastfeeding promotion. Findings Although higher socio-economic position was strongly associated with breastfeeding in ALSPAC there was little such patterning in Pelotas. In ALSPAC breastfeeding was associated with lower BP lower BMI and higher IQ adjusted for confounders but in the directions expected if due to socioeconomic patterning. In contrast in Pelotas breastfeeding was not strongly associated with BP or BMI but was associated with higher IQ. Differences in associations observed between ALSPAC and the LMIC meta-analysis were in line with those observed between ALSPAC and Pelotas but with robust evidence of heterogeneity detected between ALSPAC and the LMIC meta-analysis associations. Trial data supported the conclusions inferred by the cross-cohort comparisons which provided evidence for causal effects on IQ but not for BP or BMI. CONCLUSION: While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding breastfeeding may have causal effects on IQ. Comparing associations between populations with differing confounding structures can be used to improve causal inference in observational studies.

285 citations

Journal ArticleDOI
TL;DR: The stronger prenatal maternal associations with child dietary intake, particularly protein and fat, compared with both paternal intake associations and maternal postnatal intake associations provide some evidence for in utero programming of offspring appetite by maternal intake during pregnancy.

160 citations


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TL;DR: An adaption of Egger regression can detect some violations of the standard instrumental variable assumptions, and provide an effect estimate which is not subject to these violations, and provides a sensitivity analysis for the robustness of the findings from a Mendelian randomization investigation.
Abstract: Background: The number of Mendelian randomization analyses including large numbers of genetic variants is rapidly increasing. This is due to the proliferation of genome-wide association studies, and the desire to obtain more precise estimates of causal effects. However, some genetic variants may not be valid instrumental variables, in particular due to them having more than one proximal phenotypic correlate (pleiotropy). Methods: We view Mendelian randomization with multiple instruments as a meta-analysis, and show that bias caused by pleiotropy can be regarded as analogous to small study bias. Causal estimates using each instrument can be displayed visually by a funnel plot to assess potential asymmetry. Egger regression, a tool to detect small study bias in meta-analysis, can be adapted to test for bias from pleiotropy, and the slope coefficient from Egger regression provides an estimate of the causal effect. Under the assumption that the association of each genetic variant with the exposure is independent of the pleiotropic effect of the variant (not via the exposure), Egger’s test gives a valid test of the null causal hypothesis and a consistent causal effect estimate even when all the genetic variants are invalid instrumental variables. Results: We illustrate the use of this approach by re-analysing two published Mendelian randomization studies of the causal effect of height on lung function, and the causal effect of blood pressure on coronary artery disease risk. The conservative nature of this approach is illustrated with these examples. Conclusions: An adaption of Egger regression (which we call MR-Egger) can detect some violations of the standard instrumental variable assumptions, and provide an effect estimate which is not subject to these violations. The approach provides a sensitivity analysis for the robustness of the findings from a Mendelian randomization investigation.

3,392 citations

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TL;DR: This work introduces a technique—cross-trait LD Score regression—for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap, and uses this method to estimate 276 genetic correlations among 24 traits.
Abstract: Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment.

2,993 citations

Journal ArticleDOI
TL;DR: The remarkable range of discoveriesGWASs has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics are reviewed.
Abstract: Application of the experimental design of genome-wide association studies (GWASs) is now 10 years old (young), and here we review the remarkable range of discoveries it has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics. We predict the likely discoveries in the next 10 years, when GWASs will be based on millions of samples with array data imputed to a large fully sequenced reference panel and on hundreds of thousands of samples with whole-genome sequencing data.

2,669 citations

Journal ArticleDOI
TL;DR: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course and is currently set up as a supported access resource.
Abstract: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course. It considers multiple genetic, epigenetic, biological, psychological, social and other environmental exposures in relation to a similarly diverse range of health, social and developmental outcomes. Recruitment sought to enroll pregnant women in the Bristol area of the UK during 1990-92; this was extended to include additional children eligible using the original enrollment definition up to the age of 18 years. The children from 14541 pregnancies were recruited in 1990-92, increasing to 15247 pregnancies by the age of 18 years. This cohort profile describes the index children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks-18 years of age) and 9 clinical assessment visits (7-17 years of age). The resource comprises a wide range of phenotypic and environmental measures in addition to biological samples, genetic (DNA on 11343 children, genome-wide data on 8365 children, complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000 children) information and linkage to health and administrative records. Data access is described in this article and is currently set up as a supported access resource. To date, over 700 peer-reviewed articles have been published using ALSPAC data.

2,440 citations

Journal ArticleDOI
TL;DR: The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children.
Abstract: Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

1,902 citations