Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

GWAS in people of Middle Eastern descent reveals a locus protective of kidney function-a cross-sectional study

Mohamed, Siham A LU ; Fernadez-Tajes, Juan ; Franks, Paul W LU and Bennet, Louise LU orcid (2022) In BMC Medicine 20(1).
Abstract

BACKGROUND: Type 2 diabetes is one of the leading causes of chronic kidney failure, which increases globally and represents a significant threat to public health. People from the Middle East represent one of the largest immigrant groups in Europe today. Despite poor glucose regulation and high risk for early-onset insulin-deficient type 2 diabetes, they have better kidney function and lower rates of all-cause and cardiovascular-specific mortality compared with people of European ancestry. Here, we assessed the genetic basis of estimated glomerular filtration rate (eGFR) and other metabolic traits in people of Iraqi ancestry living in southern Sweden.

METHODS: Genome-wide association study (GWAS) analyses were performed in 1201... (More)

BACKGROUND: Type 2 diabetes is one of the leading causes of chronic kidney failure, which increases globally and represents a significant threat to public health. People from the Middle East represent one of the largest immigrant groups in Europe today. Despite poor glucose regulation and high risk for early-onset insulin-deficient type 2 diabetes, they have better kidney function and lower rates of all-cause and cardiovascular-specific mortality compared with people of European ancestry. Here, we assessed the genetic basis of estimated glomerular filtration rate (eGFR) and other metabolic traits in people of Iraqi ancestry living in southern Sweden.

METHODS: Genome-wide association study (GWAS) analyses were performed in 1201 Iraqi-born residents of the city of Malmö for eGFR and ten other metabolic traits using linear mixed-models to account for family structure.

RESULTS: The strongest association signal was detected for eGFR in CST9 (rs13037490; P value = 2.4 × 10-13), a locus previously associated with cystatin C-based eGFR; importantly, the effect (major) allele here contrasts the effect (minor) allele in other populations, suggesting favorable selection at this locus. Additional novel genome-wide significant loci for eGFR (ERBB4), fasting glucose (CAMTA1, NDUFA10, TRIO, WWC1, TRAPPC9, SH3GL2, ABCC11), quantitative insulin-sensitivity check index (METTL16), and HbA1C (CAMTA1, ME1, PAK1, RORA) were identified.

CONCLUSIONS: The genetic effects discovered here may help explain why people from the Middle East have better kidney function than those of European descent. Genetic predisposition to preserved kidney function may also underlie the observed survival benefits in Middle Eastern immigrants with type 2 diabetes.

(Less)
Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Medicine
volume
20
issue
1
article number
76
publisher
BioMed Central (BMC)
external identifiers
  • pmid:35227251
  • scopus:85125569086
ISSN
1741-7015
DOI
10.1186/s12916-022-02267-7
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
5ab591c1-b59e-4d3f-83cd-4f7b5331c498
date added to LUP
2022-03-09 13:45:28
date last changed
2024-04-18 06:16:43
@article{5ab591c1-b59e-4d3f-83cd-4f7b5331c498,
  abstract     = {{<p>BACKGROUND: Type 2 diabetes is one of the leading causes of chronic kidney failure, which increases globally and represents a significant threat to public health. People from the Middle East represent one of the largest immigrant groups in Europe today. Despite poor glucose regulation and high risk for early-onset insulin-deficient type 2 diabetes, they have better kidney function and lower rates of all-cause and cardiovascular-specific mortality compared with people of European ancestry. Here, we assessed the genetic basis of estimated glomerular filtration rate (eGFR) and other metabolic traits in people of Iraqi ancestry living in southern Sweden.</p><p>METHODS: Genome-wide association study (GWAS) analyses were performed in 1201 Iraqi-born residents of the city of Malmö for eGFR and ten other metabolic traits using linear mixed-models to account for family structure.</p><p>RESULTS: The strongest association signal was detected for eGFR in CST9 (rs13037490; P value = 2.4 × 10-13), a locus previously associated with cystatin C-based eGFR; importantly, the effect (major) allele here contrasts the effect (minor) allele in other populations, suggesting favorable selection at this locus. Additional novel genome-wide significant loci for eGFR (ERBB4), fasting glucose (CAMTA1, NDUFA10, TRIO, WWC1, TRAPPC9, SH3GL2, ABCC11), quantitative insulin-sensitivity check index (METTL16), and HbA1C (CAMTA1, ME1, PAK1, RORA) were identified.</p><p>CONCLUSIONS: The genetic effects discovered here may help explain why people from the Middle East have better kidney function than those of European descent. Genetic predisposition to preserved kidney function may also underlie the observed survival benefits in Middle Eastern immigrants with type 2 diabetes.</p>}},
  author       = {{Mohamed, Siham A and Fernadez-Tajes, Juan and Franks, Paul W and Bennet, Louise}},
  issn         = {{1741-7015}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Medicine}},
  title        = {{GWAS in people of Middle Eastern descent reveals a locus protective of kidney function-a cross-sectional study}},
  url          = {{http://dx.doi.org/10.1186/s12916-022-02267-7}},
  doi          = {{10.1186/s12916-022-02267-7}},
  volume       = {{20}},
  year         = {{2022}},
}