TY - JOUR
T1 - A population-based approach to assess the heritability and distribution of renal handling of electrolytes
AU - Moulin, Flore
AU - Ponte, Belen
AU - Pruijm, Menno
AU - Ackermann, Daniel
AU - Bouatou, Yassine
AU - Guessous, Idris
AU - Ehret, Georg
AU - Bonny, Olivier
AU - Pechère-Bertschi, Antoinette
AU - Staessen, Jan A.
AU - Paccaud, Fred
AU - Martin, Pierre Yves
AU - Burnier, Michel
AU - Vogt, Bruno
AU - Devuyst, Olivier
AU - Bochud, Murielle
N1 - Funding Information:
BP, MP, DA, IG, and GE and this study were supported by a grant from the Swiss National Science Foundation (FN 33CM30-124087). BP was also supported by the Tremplin funding and research institutional funds of the University Hospital of Geneva (departmental and Projects and Research Development funds). MB was supported by the Swiss School of Public Health Plus. OD is supported by grants from the European Community’s Seventh Framework Programme (305608 EURenOmics), the Swiss National Centre of Competence in Research Kidney Control of Homeostasis program, and the Swiss National Science Foundation (310030-146490). OB is supported by the Swiss National Center of Competence in Research Kidney Control of Homeostasis and the Swiss National Science Foundation (31003A-169850).
Publisher Copyright:
© 2017 International Society of Nephrology
PY - 2017/12
Y1 - 2017/12
N2 - The handling of electrolytes by the kidney is essential for homeostasis. However, the heritability of these processes, the first step in gene discovery, is poorly known. To help clarify this, we estimated the heritability of serum concentration, urinary excretion, renal clearance, and fractional excretion of sodium, potassium, magnesium, calcium, phosphate, and chloride in a population-based study. Nuclear families were randomly selected from the general population in Lausanne, Geneva, and Bern, Switzerland, and urine collected over 24-hour periods. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including sex, age, body mass index, and study center as covariates in the model. The 1128 participants, from 273 families, had a mean age of 47 years, body mass index of 25.0 kg/m2, and an estimated glomerular filtration rate (CKD-EPI) of 98 mL/min/1.73 m2. The heritability of serum concentration was highest for calcium, 37% and lowest for sodium, 13%. The heritability of 24-hour urine clearances, excretions, and fractional excretions ranged from 15%, 10%, and 16%, respectively, for potassium to 45%, 44%, and 51%, respectively, for calcium. All probability values were significant. The heritability for phosphate-related phenotypes was lower than that for calcium. Thus, the serum and urine concentrations as well as urinary excretion and renal handling of electrolytes are heritable in the general adult population. The phenotypic variance attributable to additive genetic factors was variable and was higher for calcium. These results pave the way for identifying genetic variants involved in electrolyte homeostasis in the general population.
AB - The handling of electrolytes by the kidney is essential for homeostasis. However, the heritability of these processes, the first step in gene discovery, is poorly known. To help clarify this, we estimated the heritability of serum concentration, urinary excretion, renal clearance, and fractional excretion of sodium, potassium, magnesium, calcium, phosphate, and chloride in a population-based study. Nuclear families were randomly selected from the general population in Lausanne, Geneva, and Bern, Switzerland, and urine collected over 24-hour periods. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including sex, age, body mass index, and study center as covariates in the model. The 1128 participants, from 273 families, had a mean age of 47 years, body mass index of 25.0 kg/m2, and an estimated glomerular filtration rate (CKD-EPI) of 98 mL/min/1.73 m2. The heritability of serum concentration was highest for calcium, 37% and lowest for sodium, 13%. The heritability of 24-hour urine clearances, excretions, and fractional excretions ranged from 15%, 10%, and 16%, respectively, for potassium to 45%, 44%, and 51%, respectively, for calcium. All probability values were significant. The heritability for phosphate-related phenotypes was lower than that for calcium. Thus, the serum and urine concentrations as well as urinary excretion and renal handling of electrolytes are heritable in the general adult population. The phenotypic variance attributable to additive genetic factors was variable and was higher for calcium. These results pave the way for identifying genetic variants involved in electrolyte homeostasis in the general population.
KW - heritability
KW - population
KW - renal function
KW - urinary phenotypes
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U2 - 10.1016/j.kint.2017.06.020
DO - 10.1016/j.kint.2017.06.020
M3 - Article
C2 - 28888328
AN - SCOPUS:85028759297
SN - 0085-2538
VL - 92
SP - 1536
EP - 1543
JO - Kidney international
JF - Kidney international
IS - 6
ER -