Interspersed repeat sequences comprise much of our DNA, although their functional effects are poorly understood. The most commonly occurring repeat is the Alu short interspersed element. New Alu insertions occur in human populations, and have been responsible for several instances of genetic disease. In this study, we sought to determine if there are instances of polymorphic Alu insertion variants that function in a common variant, common disease paradigm. We cataloged 809 polymorphic Alu elements mapping to 1,159 loci implicated in disease risk by genome-wide association study (GWAS) (P < 10−8). We found that Alu insertion variants occur disproportionately at GWAS loci (P = 0.013). Moreover, we identified 44 of these Alu elements in linkage disequilibrium (r2 > 0.7) with the trait-associated SNP. This figure represents a >20-fold increase in the number of polymorphic Alu elements associated with human phenotypes. This work provides a broader perspective on how structural variants in repetitive DNAs may contribute to human disease.

Background Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association. Objectives We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis. Methods We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies’ risk of bias in their assessment of phosphorus exposure and BP. Results We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively. Conclusions We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489.