TY - JOUR
T1 - Heritability of serum sodium concentration
T2 - Evidence for sex- and ethnic-specific effects
AU - Wilmot, Beth
AU - Saroja Voruganti, V.
AU - Chang, Yen Pei C.
AU - Fu, Yi
AU - Chen, Zhan
AU - Taylor, Herman A.
AU - Wilson, James G.
AU - Gipson, Teresa
AU - Shah, Vallabh O.
AU - Umans, Jason G.
AU - Flessner, Michael F.
AU - Hitzemann, Robert
AU - Shuldiner, Alan R.
AU - Comuzzie, Anthony G.
AU - Mcweeney, Shannon
AU - Zager, Philip G.
AU - Maccluer, Jean W.
AU - Cole, Shelley A.
AU - Cohen, David M.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Hypernatremia
KW - Hyponatremia
KW - Osmoregulation
KW - Water balance
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U2 - 10.1152/physiolgenomics.00153.2011
DO - 10.1152/physiolgenomics.00153.2011
M3 - Article
C2 - 22186255
AN - SCOPUS:84863124439
SN - 1094-8341
VL - 44
SP - 220
EP - 228
JO - Physiological genomics
JF - Physiological genomics
IS - 3
ER -