title: Maternal genetic variation accounts in part for the associations of maternal size during pregnancy with offspring cardiometabolic risk in adulthood.
abstract: BACKGROUND
  Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown.
  
  
  RESULTS
  In 1249 mother-offspring pairs recruited from the Jerusalem Perinatal Study, we used archival data to characterize ppBMI and GWG and follow-up data from offspring to assess CMR, including body mass index (BMI), waist circumference, glucose, insulin, blood pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk. We fit linear regression models to examine the associations of ppBMI and GWG with CMR traits with and without adjustment for GRS. Compared to unadjusted models, the coefficient for the association of a one-standard-deviation (SD) difference in GWG and offspring BMI decreased by 41% (95%CI -81%, -11%) from 0.847 to 0.503 and the coefficient for a 1SD difference in GWG and WC decreased by 63% (95%CI -318%, -11%) from 1.196 to 0.443. For other traits, there were no statistically significant changes in the coefficients for GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits were significantly altered by adjustment for GRS.
  
  
  CONCLUSIONS
  Maternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Pandora L
authors.initials: PL
authors.lastname: Wander
authors.affiliation: Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Hochner
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, United States of America; Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Sitlani
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Enquobahrie
authors.affiliation: Department of Statistics, University of Auckland, Auckland, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.affiliation: Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Lawrence
authors.affiliation: Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Burger
authors.affiliation: Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Savitsky
authors.affiliation: Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Manor
authors.affiliation: Department of Human Genetics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Vardiella
authors.initials: V
authors.lastname: Meiner
authors.affiliation: Institute of Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hesselson
authors.affiliation: Institute of Human Genetics, University of California San Francisco, San Francisco, California, United States of America; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America; Department of Dermatology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America; Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Friedlander
mesh_terms: D000328:Adult; D015992:Body Mass Index; D049628:Body Size / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D012307:Risk Factors; D015430:Weight Gain