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Statistical Quality Control By M Mahajan Pdfrar 41


two studies were excluded for the meta-analysis: one was a prospective observational study comparing fbt with a control intervention, but did not report serum/plasma ykl-40 levels [ 64 ], while the other reported the impact of hypertonic versus isotonic fluids, but did not report serum/plasma ykl-40 levels [ 67 ]. other study details can be found in the electronic supplemental material (additional file 1 : table s2).




Statistical Quality Control By M Mahajan Pdfrar 41


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there were no heterogeneity or publication bias between the two included meta-analyses. we first performed an iv-based meta-analysis to investigate the association between elevated serum/plasma ykl-40 and childhood bmi. two random-effects meta-analyses were conducted separately for each of the two studies. only the egger test for publication bias was statistically significant (p = 0.03), whereas the begg test for publication bias was not statistically significant (p = 0.14). the begg test for funnel plot asymmetry was not statistically significant (p = 0.06). the egger test (p = 0.03) and begg test (p = 0.06) also indicated a small level of publication bias. the combined iv-based meta-analysis of the two studies showed that elevated serum/plasma ykl-40 was associated with higher childhood bmi (standardised mean difference: 0.41; 95% ci, 0.16 to 0.66; p = 0.002) ( fig. 2).


we used 15 single nucleotide polymorphisms (snps; p 8) identified from previous genome-wide association studies (gwas) by the early growth genetics (egg) consortium as an iv for childhood bmi. this gwas included 35,668 children from 20 studies in the discovery phase and 11,873 children from 13 studies in the replication phase ( 13 ). all children included in this gwas were of european ethnic origin and 53% of the children were caucasian. the specific study population is described in the supplementary data. sex- and age-adjusted sd scores were created for childhood bmi at the latest time point (oldest age, if multiple measurements existed); the mean age was between 36.4 0.7 and 120.0 0.5 months. in the case of twin pairs, only one twin was included, either randomly or based on genotyping or imputation quality ( 13 ). the gwas study combined these 15 genome-wide significant snps into a genetic risk score that summed the number of bmi-increasing alleles weighted based on their. the genetic risk score was strongly associated with childhood bmi (p = 3.12 1010). this score explained 2.0% of the variance in childhood bmi ( 13 ), thus validating assumption 1 ( fig. 1 ).


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