Dataset Information

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

ABSTRACT:

Background

The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.

Methods

We used data from Biobank Japan (n?=?70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n?=?4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n?=?620), carotid intima-media thickness (cIMT) in adult women (n?=?781), dyslipidemia (n?=?7723), and coronary heart disease (CHD) (n?=?2374 cases and 6246 controls) in type 2 diabetes (T2D) patients.

Results

Our PRSs aggregating 84-549 genetic variants (0.251?-?103?-?75) and 3-year lipid changes (1.4?×?10^-?6?-?3?-?10?trend?=?0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI)?=?1.07 (1.03-1.11)], TG [OR (95% CI)?=?1.05 (1.01-1.09)], and LDL-C [OR (95% CI)?=?1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8?×?10^-?4?ConclusionsThe PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

SUBMITTER: Tam CHT

PROVIDER: S-EPMC7893928 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

Tam Claudia H T CHT Lim Cadmon K P CKP Luk Andrea O Y AOY Ng Alex C W ACW Lee Heung-Man HM Jiang Guozhi G Lau Eric S H ESH Fan Baoqi B Wan Raymond R Kong Alice P S APS Tam Wing-Hung WH Ozaki Risa R Chow Elaine Y K EYK Lee Ka-Fai KF Siu Shing-Chung SC Hui Grace G Tsang Chiu-Chi CC Lau Kam-Piu KP Leung Jenny Y Y JYY Tsang Man-Wo MW Kam Grace G Lau Ip-Tim IT Li June K Y JKY Yeung Vincent T F VTF Lau Emmy E Lo Stanley S Fung Samuel S Cheng Yuk-Lun YL Chow Chun-Chung CC Hu Miao M Yu Weichuan W Tsui Stephen K W SKW Huang Yu Y Lan Huiyao H Szeto Cheuk-Chun CC Tang Nelson L S NLS Ng Maggie C Y MCY So Wing-Yee WY Tomlinson Brian B Chan Juliana C N JCN Ma Ronald C W RCW

Genome medicine 20210219 1

<h4>Background</h4>The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.<h4>Methods</h4>We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-medi ...[more]

PMID: 33608049

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Project description:Aggression and callous, uncaring, and unemotional (CU) traits are clinically related behavioral constructs caused by genetic and environmental factors. We performed polygenic risk score (PRS) analyses to investigate shared genetic etiology between aggression and these three CU-traits. Furthermore, we studied interactions of PRS with smoking during pregnancy and childhood life events in relation to CU-traits. Summary statistics for the base phenotype were derived from the EAGLE-consortium genome-wide association study of children's aggressive behavior and were used to calculate individual-level genome-wide and gene-set PRS in the NeuroIMAGE target-sample. Target phenotypes were 'callousness', 'uncaring', and 'unemotional' sumscores of the Inventory of Callous-Unemotional traits. A total of 779 subjects and 1,192,414 single-nucleotide polymorphisms were available for PRS-analyses. Gene-sets comprised serotonergic, dopaminergic, glutamatergic, and neuroendocrine signaling pathways. Genome-wide PRS showed evidence of association with uncaring scores (explaining up to 1.59% of variance; self-contained Q = 0.0306, competitive-P = 0.0015). Dopaminergic, glutamatergic, and neuroendocrine PRS showed evidence of association with unemotional scores (explaining up to 1.33, 2.00, and 1.20% of variance respectively; self-contained Q-values 0.037, 0.0115, and 0.0473 respectively, competitive-P-values 0.0029, 0.0002, and 0.0045 respectively). Smoking during pregnancy related to callousness scores while childhood life events related to both callousness and unemotionality. Moreover, dopaminergic PRS appeared to interact with childhood life events in relation to unemotional scores. Our study provides evidence suggesting shared genetic etiology between aggressive behavior and uncaring, and unemotional CU-traits in children. Gene-set PRS confirmed involvement of shared glutamatergic, dopaminergic, and neuroendocrine genetic variation in aggression and CU-traits. Replication of current findings is needed.

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Dataset Information

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

Background

Methods

Results

Publications

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

Similar Datasets

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