Carlos Cotta

Gene Ordering in Microarray Data Using Parallel Memetic Algorithms

Publisher: IEEE

Date: 2005

DOI: 10.1109/ICPPW.2005.34

Birth weight and cardiometabolic risk factors: a discordant twin study in the UK Biobank.

Publisher: Cambridge University Press (CUP)

Date: 04-10-2022

DOI: 10.1017/S2040174422000538

Abstract: One of the longstanding debates in life-course epidemiology is whether an adverse intrauterine environment, often proxied by birth weight, causally increases the future risk of cardiometabolic disease. The use of a discordant twin study design, which controls for the influence of shared genetic and environmental confounding factors, may be useful to investigate whether this relationship is causal. We conducted a discordant twin study of 120 monozygotic (MZ) and 148 dizygotic (DZ) twin pairs from the UK Biobank to explore the potential causal relationships between birth weight and a broad spectrum of later-life cardiometabolic risk factors. We used a linear mixed model to investigate the association between birth weight and later-life cardiometabolic risk factors for twins, allowing for both within-pair differences and between-pair differences in birth weight. Of primary interest is the within-pair association between differences in birth weight and cardiometabolic risk factors, which could reflect an intrauterine effect on later-life risk factors. We found no strong evidence of association in MZ twins between the within-pair differences in birth weight and most cardiometabolic risk factors in later life, except for nominal associations with C-reactive protein and insulin-like growth factor 1. However, these associations were not replicated in DZ twin pairs. Our study provided no strong evidence for intrauterine effects on later-life cardiometabolic risk factors, which is consistent with previous large-scale studies of singletons testing the potential causal relationship. It does not support the hypothesis that adverse intrauterine environments increase the risk of cardiometabolic disease in later life.

Handbook of Approximation Algorithms and Metaheuristics

Publisher: Chapman and Hall/CRC

Date: 15-05-2007

DOI: 10.1201/9781420010749

Investigating a Potential Causal Relationship Between Maternal Blood Pressure During Pregnancy and Future Offspring Cardiometabolic Health

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 2022

DOI: 10.1161/HYPERTENSIONAHA.121.17701

Abstract: Observational epidemiological studies have reported that higher maternal blood pressure (BP) during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic BP and diastolic BP and a range of cardiometabolic risk factors in the offspring of up to 29 708 genotyped mother-offspring pairs from the UKB study (UK Biobank) and the HUNT study (Trøndelag Health). We conducted similar analyses in up to 21 423 father-offspring pairs from the same cohorts. We confirmed that the BP-associated genetic variants from the general population s le also had similar effects on maternal BP during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal BP is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life.

Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores

Publisher: Springer Science and Business Media LLC

Date: 02-2022

DOI: 10.1186/S12916-021-02216-W

Abstract: Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW N = 9339) and BMI at age 1 and 4 years ( N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years ( N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years ( N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates ( P difference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.

Exploring the role of genetic confounding in the association between maternal and offspring body mass index: evidence from three birth cohorts

Publisher: Oxford University Press (OUP)

Date: 10-05-2019

DOI: 10.1093/IJE/DYZ095

Abstract: Maternal pre-pregnancy body mass index (BMI) is positively associated with offspring birth weight (BW) and BMI in childhood and adulthood. Each of these associations could be due to causal intrauterine effects, or confounding (genetic or environmental), or some combination of these. Here we estimate the extent to which the association between maternal BMI and offspring body size is explained by offspring genotype, as a first step towards establishing the importance of genetic confounding. We examined the associations of maternal pre-pregnancy BMI with offspring BW and BMI at 1, 5, 10 and 15 years, in three European birth cohorts (n ≤11 498). Bivariate Genomic-relatedness-based Restricted Maximum Likelihood implemented in the GCTA software (GCTA-GREML) was used to estimate the extent to which phenotypic covariance was explained by offspring genotype as captured by common imputed single nucleotide polymorphisms (SNPs). We merged in idual participant data from all cohorts, enabling calculation of pooled estimates. Phenotypic covariance (equivalent here to Pearson’s correlation coefficient) between maternal BMI and offspring phenotype was 0.15 [95% confidence interval (CI): 0.13, 0.17] for offspring BW, increasing to 0.29 (95% CI: 0.26, 0.31) for offspring 15 year BMI. Covariance explained by offspring genotype was negligible for BW [–0.04 (95% CI: –0.09, 0.01)], but increased to 0.12 (95% CI: 0.04, 0.21) at 15 years, which is equivalent to 43% (95% CI: 15%, 72%) of the phenotypic covariance. Sensitivity analyses using weight, BMI and ponderal index as the offspring phenotype at all ages showed similar results. Offspring genotype explains a substantial fraction of the covariance between maternal BMI and offspring adolescent BMI. This is consistent with a potentially important role for genetic confounding as a driver of the maternal BMI–offspring BMI association.

Universidad De Malaga

Location: Spain

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Universidad De Málaga

Location: Spain

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University Of Bristol

Location: United Kingdom of Great Britain and Northern Ireland

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Discovery Projects - Grant ID: DP200102364

Start Date: 05-2020

End Date: 12-2024

Amount: $518,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0559755

Start Date: 06-2005

End Date: 09-2008

Amount: $218,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP120102576

Start Date: 06-2012

End Date: 12-2016

Amount: $320,000.00

Funder: Australian Research Council