A Genome-Wide Association Study of Prediabetes Status Change

被引：6

作者：

Liu, Tingting ^{[1
]}

Li, Hongjin ^{[2
]}

Conley, Yvette P. ^{[3
]}

Primack, Brian A. ^{[4
]}

Wang, Jing ^{[1
]}

Lo, Wen-Juo ^{[4
]}

Li, Changwei ^{[5
]}

机构：

[1] Florida State Univ, Coll Nursing, Tallahassee, FL USA

[2] Univ Illinois, Coll Nursing, Chicago, IL USA

[3] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA USA

[4] Univ Arkansas, Coll Educ & Hlth Profess, Fayetteville, AR USA

[5] Tulane Univ Sch Trop Med & Publ Hlth, Dept Epidemiol, New Orleans, LA 70112 USA

来源：

FRONTIERS IN ENDOCRINOLOGY | 2022年 / 13卷

基金：

美国国家卫生研究院;

关键词：

prediabetes status change; genome-wide association study; diabetes mellitus; type; 2; normoglycemia; TYPE-2 DIABETES SUSCEPTIBILITY; GENETIC ARCHITECTURE; ADIPOSE-TISSUE; HEPARANASE; EXPRESSION; PATHOPHYSIOLOGY; METAANALYSIS; INDIVIDUALS; HANDEDNESS; INSIGHTS;

D O I：

10.3389/fendo.2022.881633

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We conducted the first genome-wide association study of prediabetes status change (to diabetes or normal glycaemia) among 900 White participants of the Atherosclerosis Risk in Communities (ARIC) study. Single nucleotide polymorphism (SNP)-based analysis was performed by logistic regression models, controlling for age, gender, body mass index, and the first 3 genetic principal components. Gene-based analysis was conducted by combining SNP-based p values using effective Chi-square test method. Promising SNPs (p < 1x10-5) and genes (p < 1x10-4) were further evaluated for replication among 514 White participants of the Framingham Heart Study (FHS). To accommodate familial correlations, generalized estimation equation models were applied for SNP-based analyses in the FHS. Analysis results across ARIC and FHS were combined using inverse-variance-weighted meta-analysis method for SNPs and Fisher's method for genes. We robustly identified 5 novel genes that are associated with prediabetes status change using gene-based analyses, including SGCZ (ARIC p = 9.93x10-6, FHS p = 2.00x10-3, Meta p = 3.72x10-7) at 8p22, HPSE2 (ARIC p = 8.26x10-19, FHS p = 5.85x10-3, Meta p < 8.26x10-19) at 10q24.2, ADGRA1 (ARIC p = 1.34x10-5, FHS p = 1.13x10-3, Meta p = 2.88x10-7) at 10q26.3, GLB1L3 (ARIC p = 3.71x10-6, FHS p = 4.51x10-3, Meta p = 3.16x10-7) at 11q25, and PCSK6 (ARIC p = 6.51x10-6, FHS p = 1.10x10-2, Meta p = 1.25x10-6) at 15q26.3. eQTL analysis indicated that these genes were highly expressed in tissues related to diabetes development. However, we were not able to identify any novel locus in single SNP-based analysis. Future large scale genomic studies of prediabetes status change are warranted.

引用

页数：11

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