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Genetic Determinants of Increased Body Mass Index Partially Mediate the Effect of Elevated Birth Weight on the Increased Risk of Atrial Fibrillation.

ABSTRACT: Background: Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF. Methods: A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single-nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association studies with up to 321,223 and 1,030,836 individuals, respectively. SNPs were identified at a genome-wide significant level (p <5 × 10^-8). The inverse variance-weighted (IVW) method was employed to obtain causal estimates as our primary analysis. Sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results, and multivariable MR analysis was conducted to determine whether this association was mediated by the body mass index (BMI). Results: In total, 144 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.27, 95% CI = 1.14-1.40, p = 5.70 × 10^-6). All the results in sensitivity analyses were consistent with the primary result. The effect of BW on AF was attenuated when adjusted for BMI (OR = 1.16, 95% CI = 1.01-1.33, p = 0.04). Conclusions: This study indicated that elevated BW was significantly associated with increased lifelong risk of AF, which may be partially mediated by BMI.

SUBMITTER: Chen S

PROVIDER: S-EPMC8377229 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesWeight at birth is usually considered as an indicator of the health status of a given society. As a result this study was designed to investigate the association between birth weight and maternal factors such as gestational weight gain, pre-pregnancy BMI and socio-economic status in Northern Ghana.MethodsThe study was a facility-based cross-sectional survey conducted in two districts in the Northern region of Ghana. These districts were purposively sampled to represent a mix of urban, peri-urban and rural population. The current study included 419 mother-infant pairs who delivered at term (37-42 weeks). Mother's height, pre-pregnancy weight and weight changes were generated from the antenatal records. Questionnaires were administered to establish socio-economic and demographic information of respondents. Maternal factors associated with birth weight were examined using multiple and univariate regressions.ResultsThe mothers were generally well nourished before conception (Underweight 3.82%, Normal 57.76%, Overweight 25.06% and Obesity 13.37%) but approximately half of them could not gain adequate weight according to Institute of Medicine recommendations (Low weight gain 49.64%, Adequate weight gain 42.96% and Excessive weight gain 7.40%). Infants whose mothers had excess weight gain were 431g (95% CI 18-444) heavier compared to those whose mothers gained normal weight, while those whose mothers gained less were 479g (95% CI -682- (-276) lighter. Infants of mothers who were overweight and obese before conception were 246g (95% CI 87-405) and 595g (95% CI 375-815) respectively heavier than those of normal mothers, whereas those whose mothers were underweight were 305g (95% CI -565 -(-44) lighter. The mean birth weight observed was 2.98 ± 0.68 kg.ConclusionOur findings show that pre-pregnancy body mass index and weight gain during pregnancy influence birth weight. Therefore, emphasis should be placed on counseling and assisting pregnant women to stay within the recommended weight gain ranges.

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Genetic Determinants of Increased Body Mass Index Partially Mediate the Effect of Elevated Birth Weight on the Increased Risk of Atrial Fibrillation.

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