title: Heritability of serum sodium concentration: evidence for sex- and ethnic-specific effects.
abstract: 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 × 10 ⁻⁷), SHFS (0.59 ± 0.05, P = 9.4 × 10⁻⁴⁶), and GKDZI (0.46 ± 0.15, P = 1.7 × 10⁻⁴), and male participants in HAPI (0.18 ± 0.12, P = 0.03) and SHFS (0.67 ± 0.07, P = 5.4 × 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.
authors.affiliation: Division of Nephrology & Hypertension, Departments of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Wilmot
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Yen-Pei C
authors.initials: YP
authors.lastname: Chang
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.forename: Zhan
authors.initials: Z
authors.lastname: Chen
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Teresa
authors.initials: T
authors.lastname: Gipson
authors.forename: Vallabh O
authors.initials: VO
authors.lastname: Shah
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Michael F
authors.initials: MF
authors.lastname: Flessner
authors.forename: Robert
authors.initials: R
authors.lastname: Hitzemann
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Shannon
authors.initials: S
authors.lastname: McWeeney
authors.forename: Philip G
authors.initials: PG
authors.lastname: Zager
authors.forename: Jean W
authors.initials: JW
authors.lastname: Maccluer
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: David M
authors.initials: DM
authors.lastname: Cohen
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D061365:Amish / Q000235:genetics*; D000704:Analysis of Variance; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D019655:Quantitative Trait, Heritable; D012737:Sex Factors; D012964:Sodium / Q000097:blood*; D014882:Water-Electrolyte Balance / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D012964:Sodium