Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations

نویسندگان

  • Christopher A. Haiman
  • Megan D. Fesinmeyer
  • Kylee L. Spencer
  • Petra Bůžková
  • V. Saroja Voruganti
  • Peggy Wan
  • Jeff Haessler
  • Nora Franceschini
  • Kristine R. Monroe
  • Barbara V. Howard
  • Rebecca D. Jackson
  • Jose C. Florez
  • Laurence N. Kolonel
  • Steven Buyske
  • Robert J. Goodloe
  • Simin Liu
  • JoAnn E. Manson
  • James B. Meigs
  • Kevin Waters
  • Kenneth J. Mukamal
  • Sarah A. Pendergrass
  • Peter Shrader
  • Lynne R. Wilkens
  • Lucia A. Hindorff
  • Jose Luis Ambite
  • Kari E. North
  • Ulrike Peters
  • Dana C. Crawford
  • Loic Le Marchand
  • James S. Pankow
چکیده

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups

It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that estab...

متن کامل

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

The majority of GWAS of T2D susceptibility have been undertaken in populations of European ancestry1–5, predominantly because of existing infrastructure, sample availability and relatively poor coverage by many of the earliest genome-wide genotyping arrays of common genetic variation in other major ethnic groups6. However, populations of European ancestry constitute only a subset of human genet...

متن کامل

P-167: Association between Pregnancy Dietary Iron Intake and Gestational Diabetes Mellitus

Background: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications affecting approximately 7% of all pregnancies and up to 14% of pregnancies in high-risk populations. Although, dietary iron intake is one of preventive factors for Iron deficiency which leads to less preterm delivery, prematurity, and SGA but iron is a strong pro-oxidant and high body iron levels c...

متن کامل

Role of Established Type 2 Diabetes–Susceptibility Genetic Variants in a High Prevalence American Indian Population

Several single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM) have been identified, but there is little information on their role in populations at high risk for T2DM. We genotyped SNPs at 63 T2DM loci in 3,421 individuals from a high-risk American Indian population. Nominally significant (P < 0.05) associations were observed at nine SNPs in a direction consiste...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 61  شماره 

صفحات  -

تاریخ انتشار 2012