2016
DOI: 10.1002/ijc.30206
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Abstract: Circulating insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome‐wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replica… Show more

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Cited by 26 publications
(29 citation statements)
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“…We conducted various sensitivity analyses to assess the possible influence of horizontal pleiotropy on our causal estimates, and our results were robust to these various tests. The possibility exists, however, that our results may have been influenced by pleiotropy from other unmeasured IGF axis components 30 . To date, the only GWAS analyses that have been conducted for components of this pathway are for IGF-1 and IGFBP-3, therefore the extent of this possible pleiotropy within the IGF axis is uncertain.…”
Section: Discussionmentioning
confidence: 88%
“…We conducted various sensitivity analyses to assess the possible influence of horizontal pleiotropy on our causal estimates, and our results were robust to these various tests. The possibility exists, however, that our results may have been influenced by pleiotropy from other unmeasured IGF axis components 30 . To date, the only GWAS analyses that have been conducted for components of this pathway are for IGF-1 and IGFBP-3, therefore the extent of this possible pleiotropy within the IGF axis is uncertain.…”
Section: Discussionmentioning
confidence: 88%
“…The SNPs used in these analyses are not ideal instruments for single IGF peptides: several that affect IGF1 also appear to alter IGFBP3 concentrations and vice versa, and perhaps also influence circulating IGF2 (for which we did not find suitable variants to instrument specifically). 37 Therefore, variants are not indicating AD risk differences attributable to one IGF molecule specifically, although sensitivity analyses using subsets of SNPs that were carefully assessed for magnitudes of effects on each peptide can help in this respect. Moreover, effects of variants on multiple IGF peptides may not invalidate their use as instruments for IGF axis activity as a whole.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, effects of variants on multiple IGF peptides may not invalidate their use as instruments for IGF axis activity as a whole. 37 We did not address the potential for insulin to influence AD risk; a point of relevance, given that insulin binds to IGF receptors. However, a previous MR study found that AD risk did not differ by genetically predicted variation in insulin.…”
Section: Discussionmentioning
confidence: 99%
“…The genotyping methods have previously been described by Bonilla and colleagues [ 18 ]. Genome-wide genotypic data for the children were generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute (Cambridge, UK) and the Laboratory Corporation of America (Burlington, NC, USA) with support from 23andMe (Mountain View, CA, USA) using the Illumina HumanHap550 quad chip.…”
Section: Methodsmentioning
confidence: 99%