Sex Differences in the Genetic Relationship Between Type 2 Diabetes and Cataract : Insights From East Asian and European Populations
Chen, Hongwei ; You, Danming ; Zhou, Liangbin and Zhang, Haoyang LU
(2025)
In Medicine Advances
3(4).
p.319-330
- Abstract
Background: Type 2 diabetes (T2D) is a well-established risk factor for cataract. However, whether the causal effect on cataract differs by sex remains unclear. Determining whether this causal effect differs by sex could help resolve discrepancies in epidemiological studies regarding cataract risk in populations with diabetes. Methods: Using summary statistics of East Asian and European populations from sex-stratified genome-wide association studies, we conducted sex-stratified analyses to investigate the genetic relationships between T2D and cataract. We began by identifying sex-dimorphic single nucleotide polymorphisms (sdSNPs) by comparing genetic effect sizes between males and females. Next, we estimated sex-specific genetic... (More)
Background: Type 2 diabetes (T2D) is a well-established risk factor for cataract. However, whether the causal effect on cataract differs by sex remains unclear. Determining whether this causal effect differs by sex could help resolve discrepancies in epidemiological studies regarding cataract risk in populations with diabetes. Methods: Using summary statistics of East Asian and European populations from sex-stratified genome-wide association studies, we conducted sex-stratified analyses to investigate the genetic relationships between T2D and cataract. We began by identifying sex-dimorphic single nucleotide polymorphisms (sdSNPs) by comparing genetic effect sizes between males and females. Next, we estimated sex-specific genetic relationships between T2D and cataract using linkage disequilibrium score regression and Mendelian randomization approaches. To identify the functional genes that underlie the observed sex difference, we used summary-data-based Mendelian randomization and colocalization analyses. Results: In East Asians, we identified 88 T2D-related and 32 cataract-related sdSNPs. Subsequent Mendelian randomization analyses revealed a potential causal effect of T2D on cataract, with a stronger effect observed in males than in females. Summary-data-based Mendelian randomization and colocalization analyses identified several male-specific candidate genes, including RPL6, PTPN11, and RPH3A, that linked T2D to cataract in East Asians. In contrast, no significant sex-specific causal effect was detected in the European population. Conclusions: Our findings provide novel evidence for sex-specific genetic relationships between T2D and cataract, particularly in East Asians, and highlight the importance of considering population-specific genetic heterogeneity in causal inference and disease prevention strategies.
(Less)
- author
- Chen, Hongwei
; You, Danming
; Zhou, Liangbin
and Zhang, Haoyang
LU
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cataract, genome-wide association study, mendelian randomization, sex differences, type 2 diabetes
- in
- Medicine Advances
- volume
- 3
- issue
- 4
- pages
- 12 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:105025252214
- ISSN
- 2834-4391
- DOI
- 10.1002/med4.70045
- language
- English
- LU publication?
- yes
- id
- 9b0bbe91-642a-4221-bfe6-6c3a6d28b127
- date added to LUP
- 2026-02-12 16:13:37
- date last changed
- 2026-02-13 03:51:29
@article{9b0bbe91-642a-4221-bfe6-6c3a6d28b127,
abstract = {{<p>Background: Type 2 diabetes (T2D) is a well-established risk factor for cataract. However, whether the causal effect on cataract differs by sex remains unclear. Determining whether this causal effect differs by sex could help resolve discrepancies in epidemiological studies regarding cataract risk in populations with diabetes. Methods: Using summary statistics of East Asian and European populations from sex-stratified genome-wide association studies, we conducted sex-stratified analyses to investigate the genetic relationships between T2D and cataract. We began by identifying sex-dimorphic single nucleotide polymorphisms (sdSNPs) by comparing genetic effect sizes between males and females. Next, we estimated sex-specific genetic relationships between T2D and cataract using linkage disequilibrium score regression and Mendelian randomization approaches. To identify the functional genes that underlie the observed sex difference, we used summary-data-based Mendelian randomization and colocalization analyses. Results: In East Asians, we identified 88 T2D-related and 32 cataract-related sdSNPs. Subsequent Mendelian randomization analyses revealed a potential causal effect of T2D on cataract, with a stronger effect observed in males than in females. Summary-data-based Mendelian randomization and colocalization analyses identified several male-specific candidate genes, including RPL6, PTPN11, and RPH3A, that linked T2D to cataract in East Asians. In contrast, no significant sex-specific causal effect was detected in the European population. Conclusions: Our findings provide novel evidence for sex-specific genetic relationships between T2D and cataract, particularly in East Asians, and highlight the importance of considering population-specific genetic heterogeneity in causal inference and disease prevention strategies.</p>}},
author = {{Chen, Hongwei and You, Danming and Zhou, Liangbin and Zhang, Haoyang}},
issn = {{2834-4391}},
keywords = {{cataract; genome-wide association study; mendelian randomization; sex differences; type 2 diabetes}},
language = {{eng}},
number = {{4}},
pages = {{319--330}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Medicine Advances}},
title = {{Sex Differences in the Genetic Relationship Between Type 2 Diabetes and Cataract : Insights From East Asian and European Populations}},
url = {{http://dx.doi.org/10.1002/med4.70045}},
doi = {{10.1002/med4.70045}},
volume = {{3}},
year = {{2025}},
}