Heritability of serum sodium concentration: evidence for sex- and ethnic-specific effects.

MedStar author(s):
Citation: Physiological Genomics. 44(3):220-8, 2012 Feb 13.PMID: 22186255Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Comparative Study | Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *African Americans/ge [Genetics] | *Amish/ge [Genetics] | *European Continental Ancestry Group/ge [Genetics] | *Indians, North American/ge [Genetics] | *Quantitative Trait, Heritable | *Sodium/bl [Blood] | *Water-Electrolyte Balance/ge [Genetics] | Age Factors | Analysis of Variance | Cohort Studies | Female | Humans | Male | Sex FactorsYear: 2012ISSN:
  • 1094-8341
Name of journal: Physiological genomicsAbstract: Serum sodium concentration is the clinical index of systemic water balance. Although disordered water balance is common and morbid, little is known about genetic effects on serum sodium concentration at the population level. Prior studies addressed only participants of European descent and either failed to demonstrate significant heritability or showed only modest effect. We investigated heritability of serum sodium concentration in large cohorts reflecting a range of races/ethnicities, including the Framingham Heart Study (FHS, non-Hispanic Caucasian), the Heredity and Phenotype Intervention Heart Study (HAPI, Amish Caucasian), the Jackson Heart Study (JHS, African American), the Strong Heart Family Study (SHFS, American Indian), and the Genetics of Kidney Disease in Zuni Indians Study (GKDZI, American Indian). Serum sodium was transformed for the osmotic effect of glucose, and participants with markedly elevated glucose or reduced estimated glomerular filtration rate (eGFR) were excluded. Using a standard variance components method, incorporating covariates of age, glucose, and eGFR, we found heritability to be high in African American and American Indian populations and much more modest in non-Hispanic Caucasian populations. Estimates among females increased after stratification on sex and were suggestive among female participants in FHS (0.18 +/- 0.12, P = 0.057) and male participants in JHS (0.24 +/- 0.16, P = 0.067) and statistically significant among female participants in JHS (0.44 +/- 0.09, P = 1 x 10 -7), SHFS (0.59 +/- 0.05, P = 9.4 x 10-46), and GKDZI (0.46 +/- 0.15, P = 1.7 x 10-4), and male participants in HAPI (0.18 +/- 0.12, P = 0.03) and SHFS (0.67 +/- 0.07, P = 5.4 x 10-26). Exclusion of diuretic users increased heritability among females and was significant in all cohorts where data were available. In aggregate, these data strongly support the heritability of systemic water balance and underscore sex and ethnicity-specific effects.All authors: Chang YP, Chen Z, Cohen DM, Cole SA, Comuzzie AG, Flessner MF, Fu Y, Gipson T, Hitzemann R, Maccluer JW, McWeeney S, Shah VO, Shuldiner AR, Taylor HA, Umans JG, Voruganti VS, Wilmot B, Wilson JG, Zager PGFiscal year: FY2012Digital Object Identifier: Date added to catalog: 2013-09-17
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Journal Article MedStar Authors Catalog Article 22186255 Available 22186255

Serum sodium concentration is the clinical index of systemic water balance. Although disordered water balance is common and morbid, little is known about genetic effects on serum sodium concentration at the population level. Prior studies addressed only participants of European descent and either failed to demonstrate significant heritability or showed only modest effect. We investigated heritability of serum sodium concentration in large cohorts reflecting a range of races/ethnicities, including the Framingham Heart Study (FHS, non-Hispanic Caucasian), the Heredity and Phenotype Intervention Heart Study (HAPI, Amish Caucasian), the Jackson Heart Study (JHS, African American), the Strong Heart Family Study (SHFS, American Indian), and the Genetics of Kidney Disease in Zuni Indians Study (GKDZI, American Indian). Serum sodium was transformed for the osmotic effect of glucose, and participants with markedly elevated glucose or reduced estimated glomerular filtration rate (eGFR) were excluded. Using a standard variance components method, incorporating covariates of age, glucose, and eGFR, we found heritability to be high in African American and American Indian populations and much more modest in non-Hispanic Caucasian populations. Estimates among females increased after stratification on sex and were suggestive among female participants in FHS (0.18 +/- 0.12, P = 0.057) and male participants in JHS (0.24 +/- 0.16, P = 0.067) and statistically significant among female participants in JHS (0.44 +/- 0.09, P = 1 x 10 -7), SHFS (0.59 +/- 0.05, P = 9.4 x 10-46), and GKDZI (0.46 +/- 0.15, P = 1.7 x 10-4), and male participants in HAPI (0.18 +/- 0.12, P = 0.03) and SHFS (0.67 +/- 0.07, P = 5.4 x 10-26). Exclusion of diuretic users increased heritability among females and was significant in all cohorts where data were available. In aggregate, these data strongly support the heritability of systemic water balance and underscore sex and ethnicity-specific effects.

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