Heritability and individuality of the plasma sodium concentration: a twin study in the United States veteran population.
Heritability and individuality of the plasma sodium concentration: a twin study in the United States veteran population.
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血浆钠浓度的遗传性和个体性：美国退伍军人群体的一项双胞胎研究。
DOI：
10.1152/ajprenal.00581.2018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Cohen,DavidM
中科院分区：
文献类型：
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作者：
Timmons,AndrewK;Korpak,AnnaM;Tan,Jenny;Moore,KathrynP;Liu,CindyH;Forsberg,ChristopherW;Goldberg,Jack;Smith,NicholasL;Cohen,DavidM
对水平衡的群体遗传学知之甚少。最近的一项关于血浆钠浓度的全元基因组关联研究确定了具有高生物学可遗传性的新基因座，但表型的遗传性从未在欧洲血统中令人信服地显示。本研究将越南时代双胞胎登记处与退伍军人事务部VistA患者护理临床数据库联系起来。参与者（n= 2，370，59.6%为单卵双胞胎，40.4%为双卵双胞胎）在1999年10月至2017年3月期间进行了7次（四分位数间距：3 - 14）血浆钠测定。在排除了514对仅进行了一次血浆钠测定的双胞胎后，所有双胞胎平均血浆钠浓度的遗传度分别为0.41（95%置信区间：0.35 - 0.46）和0.49（95%置信区间：0.43 - 0.54）。高加索人（n= 1，958）和非洲裔美国人（n= 268）双胞胎的遗传力分别为0.41（95%置信区间：0.34 - 0.47）和0.36（95%置信区间：0.17 - 0.52）。排除那些服用已知会影响全身水平衡的药物的双胞胎的数据没有影响。本研究在多个种族组中新检测到实质性遗传性的能力可能是队列大小和相关性、排除受血糖升高和/或肾小球滤过率降低混淆的钠测定、血浆钠转化为血糖的独立渗透效应以及在数年内对每个个体使用多个实验室测定的函数。个体水平的血浆钠浓度表现出纵向稳定性（即，个性）;无论测定次数多少，个体水平平均值与总体平均值的差异程度都很大。总的来说，这些数据建立了欧洲血统的血浆钠浓度的遗传性，并证实了其个性。
Little is known about the population genetics of water balance. A recent meta-genome-wide association study on plasma sodium concentration identified novel loci of high biological plausibility, yet heritability of the phenotype has never been convincingly shown in European ancestry. The present study linked the Vietnam Era Twin Registry with the Department of Veterans Affairs VistA patient care clinical database. Participants (n= 2,370, 59.6% monozygotic twins and 40.4% dizygotic twins) had a median of seven (interquartile range: 3−14) plasma sodium determinations between October 1999 and March 2017. Heritability of the mean plasma sodium concentration among all twins was 0.41 (95% confidence interval: 0.35−0.46) and 0.49 (95% confidence interval: 0.43−0.54) after exclusion of 514 twins with only a single plasma sodium determination. Heritability among Caucasian (n= 1,958) and African-American (n= 268) twins was 0.41 (95% confidence interval: 0.34−0.47) and 0.36 (95% confidence interval: 0.17−0.52), respectively. Exclusion of data from twins who had been prescribed medications known to impact systemic water balance had no effect. The ability of the present study to newly detect substantial heritability across multiple racial groups was potentially a function of the cohort size and relatedness, exclusion of sodium determinations confounded by elevated plasma glucose and/or reduced glomerular filtration rate, transformation of plasma sodium for the independent osmotic effect of plasma glucose, and use of multiple laboratory determinations per individual over a period of years. Individual-level plasma sodium concentration exhibited longitudinal stability (i.e., individuality); the degree to which individual-level means differed from the population mean was substantial, irrespective of the number of determinations. In aggregate, these data establish the heritability of plasma sodium concentration in European ancestry and corroborate its individuality.