title: Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men.
abstract: The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001-0.009, odds ratios [ORs] 1.27-1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 x 10(-4), OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.
authors.affiliation: Program in Genomics and Division of Endocrinology, Children's Hospital, Boston, Massachusetts 021115, USA.
authors.forename: Catarina D
authors.initials: CD
authors.lastname: Campbell
authors.forename: Helen N
authors.initials: HN
authors.lastname: Lyon
authors.forename: James
authors.initials: J
authors.lastname: Nemesh
authors.forename: Jared A
authors.initials: JA
authors.lastname: Drake
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Ardlie
authors.forename: Leif C
authors.initials: LC
authors.lastname: Groop
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
mesh_terms: D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D012016:Reference Values; D012727:Sex Characteristics
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor