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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Exploring the interaction between SNP genotype and postmenopausal hormone therapy effects on stroke risk
Ying Huang1, Dennis G Ballinger2, Renee Stokowski3
1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
Genome Medicine
|July 17, 2012
Summary
Postmenopausal hormone therapy (HT) interacts with specific gene variations (F13A1, PCSK9) to influence stroke risk. This genotype-environment interaction research identifies novel genomic regions for further stroke risk investigation.
Area of Science:
- Genetics
- Epidemiology
- Women's Health
Background:
- Genome-wide association studies (GWAS) identify some stroke risk regions, but explain limited familial aggregation.
- Genotype by environment interactions may further explain stroke risk.
- The Women's Health Initiative (WHI) trial offers a setting to study genotype-hormone therapy (HT) interactions for stroke risk.
Purpose of the Study:
- To evaluate genotype-HT interactions on postmenopausal stroke risk.
- To identify specific genetic variants and hormonal exposures influencing stroke risk.
Main Methods:
- Examined HT by genotype interactions for 392 candidate SNPs and 2,371 protein concentration-associated SNPs.
- Included 2,045 postmenopausal women with stroke and matched controls from the WHI trial and observational study.
- Employed a two-stage procedure with case-only analysis for interaction testing.
Main Results:
- Identified two SNPs in the coagulation factor XIII subunit A (F13A1) region and two SNPs in the proprotein convertase subtilisin kexin 9 (PCSK9) region with false discovery rate <0.05.
- Found significant stroke risk interaction between F13A1 SNPs and estrogen plus progestin (E+P) for ischemic stroke.
- Suggested interactions between PCSK9 SNPs and E+P or estrogen-alone treatments.
Conclusions:
- Genotype by environment interactions can define genomic regions relevant to stroke risk.
- Two-stage analysis in postmenopausal women generated novel hypotheses for F13A1 and PCSK9 regions.
- Findings highlight potential effects of hormonal exposures on postmenopausal stroke risk, requiring validation.
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