title: Increased identification of novel variants in type 2 diabetes, birth weight and their pleiotropic loci.
abstract: BACKGROUND
  Clinical and epidemiological findings point to an association between type 2 diabetes (T2D) and low birth weight. However, the nature of the relationship is largely unknown. The aim of this study was to identify novel single nucleotide polymorphisms (SNPs) in T2D and birth weight, and their pleiotropic loci.
  
  
  METHODS
  A pleiotropy-informed conditional false discovery rate (cFDR) method was applied to two independent genome-wide association studies (GWAS) summary statistics of T2D (n = 149 821) and birth weight (n = 26 836).
  
  
  RESULTS
  A conditional Q-Q plot showed strong enrichment of genetic variants in T2D conditioned on different levels of association with birth weight. 133 T2D-associated SNPs, including 120 novel SNPs, were identified with a significance threshold of cFDR < 0.05; 13 significant birth weight-associated SNPs, including 12 novel SNPs (cFDR < 0.05) were identified. Conjunctional cFDR (ccFDR) analysis identified nine pleiotropic loci, including seven novel loci, shared by both T2D and birth weight (ccFDR < 0.05). Two novel SNPs located at the CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1; rs1012635; cFDR < 0.05) and adenylate cyclase 5 (ADCY5; rs4677887; cFDR < 0.05) genes are of note. These two genes increase the risk of T2D and low birth weight through the pathway of the "fetal insulin hypothesis."
  
  
  CONCLUSIONS
  Several pleiotropic loci were identified between T2D and birth weight by leveraging GWAS results. The results make it possible to explain a greater proportion of trait heritability and improve our understanding of the shared pathophysiology between T2D and birth weight.
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.|Department of Endocrinology and Metabolism, Affiliated Nanhai Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Biostatistics and Bioinformatics, Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Greenbaum
authors.affiliation: Department of Endocrinology and Metabolism, Affiliated Nanhai Hospital of Southern Medical University, Guangzhou, China.
authors.forename: You-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Xia-Fang
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Rou
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Rehabilitation, General Hospital of Guangzhou Military Command of Chinese PLA, Guangzhou, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Deng
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.|Department of Biostatistics and Bioinformatics, Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D066264:Datasets as Topic; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005189:False Positive Reactions; D053263:Gene Regulatory Networks; D056426:Genetic Loci; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000592:standards / Q000706:statistics & numerical data / Q000639:trends*; D006801:Humans; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide
keywords: 2型糖尿病; birth weight; genome-wide association study; pleiotropy; type 2 diabetes; 全基因组联分析; 出生体重; 基因多效性