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GWAS Study

Exome-wide analysis identifies three low-frequency missense variants associated with pancreatic cancer risk in Chinese populations.

Chang J, Tian J, Zhu Y et al.

30206226 PubMed ID
GWAS Study Type
11690 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

CJ
Chang J
TJ
Tian J
ZY
Zhu Y
ZR
Zhong R
ZK
Zhai K
LJ
Li J
KJ
Ke J
HQ
Han Q
LJ
Lou J
CW
Chen W
ZB
Zhu B
SN
Shen N
ZY
Zhang Y
GY
Gong Y
YY
Yang Y
ZD
Zou D
PX
Peng X
ZZ
Zhang Z
ZX
Zhang X
HK
Huang K
YM
Yang M
WL
Wang L
WC
Wu C
LD
Lin D
MX
Miao X
Chapter II

Abstract

Summary of the research findings

Germline coding variants have not been systematically investigated for pancreatic ductal adenocarcinoma (PDAC). Here we report an exome-wide investigation using the Illumina Human Exome Beadchip with 943 PDAC cases and 3908 controls in the Chinese population, followed by two independent replicate samples including 2142 cases and 4697 controls. We identify three low-frequency missense variants associated with the PDAC risk: rs34309238 in PKN1 (OR = 1.77, 95% CI: 1.48-2.12, P = 5.35 × 10-10), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50-2.27, P = 4.34 × 10-9), and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72-3.16, P = 4.21 × 10-8). Functional analyses show that the PKN1 rs34309238 variant significantly increases the level of phosphorylated PKN1 and thus enhances PDAC cells' proliferation by phosphorylating and activating the FAK/PI3K/AKT pathway. These findings highlight the significance of coding variants in the development of PDAC and provide more insights into the prevention of this disease.

943 Chinese ancestry cases, 3,908 Chinese ancestry controls

Chapter III

Study Statistics

Key metrics and study information

11690
Total Participants
GWAS
Study Type
Yes
Replicated
2,142 Chinese ancestry cases, 4,697 Chinese ancestry controls
Replication Participants
East Asian
Ancestry
China
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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