Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, Massachusetts.
Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, Massachusetts; Department of Anesthesia, Center of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
J Surg Res. 2024 Nov;303:287-294. doi: 10.1016/j.jss.2024.09.028. Epub 2024 Oct 10.
Pancreas divisum (PD) is a common congenital anomaly of the pancreas, but its genetic basis remains unknown. The purpose of this genome-wide association study was to identify genetic loci associated with PD.
Using the Mass General Brigham Biobank, patients diagnosed with PD were identified. Quality control and imputation were performed using standard approaches. Single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 5% were tested for association with PD using mixed linear model-based association analysis. The significance threshold was set at 5 × 10.
A total of 13,940 subjects were included, of which 251 (1.8%) were diagnosed with PD. A genetic locus in chromosome 3q29 was found to be associated with PD (lead SNP rs3850646, MAF = 34.6% vs. MAF = 26.4%, beta = 0.0106, P = 1.47 × 10). The identified locus is located in the phosphatidylinositol glycan anchor biosynthesis class Xand p21 activated kinase 2genes. The heritability of PD was estimated at 27.5%. (Expression quantitative trait loci) and chromatin interaction analysis found 12 genes whose expression may be regulated by SNPs in this genomic locus.
The results of this study suggest that a genetic locus at 3q29 is associated with PD. This locus is in the phosphatidylinositol glycan anchor biosynthesis class X and p21 activated kinase 2 genes. Twelve candidate genes were identified whose expression may be regulated by this locus. These findings may help us understand both normal and aberrant pancreatic development and may aid in clinical evaluation and genetic counseling of patients with PD and associated diseases, such as acute pancreatitis.
胰腺分裂症（PD）是一种常见的胰腺先天性异常，但其遗传基础尚不清楚。本全基因组关联研究的目的是确定与 PD 相关的遗传位点。
使用麻省总医院布列根生物银行，确定了被诊断为 PD 的患者。使用标准方法进行质量控制和单倍型推断。使用基于混合线性模型的关联分析，对次要等位基因频率（MAF）≥5%的单核苷酸多态性（SNP）与 PD 进行关联检验。显著性阈值设定为 5×10。
共纳入 13940 例受试者，其中 251 例（1.8%）被诊断为 PD。发现染色体 3q29 上的一个遗传位点与 PD 相关（先导 SNP rs3850646，MAF=34.6%比 MAF=26.4%，β=0.0106，P=1.47×10）。鉴定的位点位于磷脂酰肌醇聚糖锚生物合成类 X 和 p21 激活激酶 2 基因中。PD 的遗传率估计为 27.5%。（表达数量性状基因座）和染色质相互作用分析发现 12 个基因，其表达可能受该基因组位点 SNP 的调控。
本研究结果表明，3q29 上的一个遗传位点与 PD 相关。该位点位于磷脂酰肌醇聚糖锚生物合成类 X 和 p21 激活激酶 2 基因中。鉴定出 12 个候选基因，其表达可能受该位点调控。这些发现可能有助于我们了解正常和异常的胰腺发育，并可能有助于 PD 及相关疾病（如急性胰腺炎）患者的临床评估和遗传咨询。
