Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid.
Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid.
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钙、镁和尿酸 24 小时尿液排泄的全基因组关联研究。
DOI：
10.1016/j.mayocpiqo.2019.08.007
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Lieske,JohnC
中科院分区：
文献类型：
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作者：
Ware,ErinB;Smith,JenniferA;Zhao,Wei;Ganesvoort,RonT;Curhan,GaryC;Pollak,Martin;Mount,DavidB;Turner,StephenT;Chen,Guotao;Shah,RonakJagdeep;Kardia,SharonLR;Lieske,JohnC
ObjectivesThe urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined.MethodsGenome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume).ResultsOne region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was nearTRPM6, whose protein product mediates magnesium transport in the colon and kidney, andC9orf40,C9orf41,NMRK1, andOSTF1(rs1176815;P=1.70×10–14, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20;P=1.12×10–8) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs.ConclusionCommon variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.
