title: Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after Roux-en-Y gastric bypass surgery.
abstract: BACKGROUND
  Roux-en-Y gastric bypass (RYGB) is among the most effective treatments for extreme obesity and obesity-related complications. However, despite its potential efficacy, many patients do not achieve and/or maintain sufficient weight loss.
  
  
  OBJECTIVE
  Our objective was to identify genetic factors underlying the variability in weight loss outcomes after RYGB surgery.
  
  
  METHODS
  We conducted a genome-wide association study using a 2-stage phenotypic extreme study design.
  
  
  METHODS
  Patients were recruited from a comprehensive weight loss program at an integrated health system.
  
  
  METHODS
  Eighty-six obese (body mass index >35 kg/m(2)) patients who had the least percent excess body weight loss (%EBWL) and 89 patients who had the most %EBWL at 2 years after surgery were genotyped using Affymetrix version 6.0 single-nucleotide polymorphism (SNP) arrays. A second group from the same cohort consisting of 164 patients in the lower quartile of %EBWL and 169 from the upper quartile were selected for evaluation of candidate regions using custom SNP arrays.
  
  
  METHODS
  We performed RYGB surgery.
  
  
  METHODS
  We assessed %EBWL at 2 years after RYGB and SNPs.
  
  
  RESULTS
  We identified 111 SNPs in the first-stage analysis whose frequencies were significantly different between 2 phenotypic extremes of weight loss (allelic χ(2) test P < .0001). Linear regression of %EBWL at 2 years after surgery revealed 17 SNPs that approach P < .05 in the validation stage and cluster in or near several genes with potential biological relevance including PKHD1, HTR1A, NMBR, and IGF1R.
  
  
  CONCLUSIONS
  This is the first genome-wide association study of weight loss response to RYGB. Variation in weight loss outcomes after RYGB may be influenced by several common genetic variants.
authors: Department of Surgery, New York University Langone Medical Center, New York, New York 10016, USA.
authors: Erica S
authors: ES
authors: Rinella
authors: Christopher
authors: C
authors: Still
authors: Yongzhao
authors: Y
authors: Shao
authors: G Craig
authors: GC
authors: Wood
authors: Xin
authors: X
authors: Chu
authors: Brenda
authors: B
authors: Salerno
authors: Glenn S
authors: GS
authors: Gerhard
authors: Harry
authors: H
authors: Ostrer
mesh_terms: D015992:Body Mass Index; D005260:Female; D015390:Gastric Bypass; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015431:Weight Loss
references: Cell. 2009 Sep 4;138(5):976-89
references: 19737523
references: Diabetes. 2004 May;53(5):1399-402
references: 15111512
references: Arch Surg. 2003 May;138(5):541-5; discussion 545-6
references: 12742960
references: Obes Surg. 2011 Nov;21(11):1724-30
references: 21509481
references: J Gastroenterol Hepatol. 2010 Aug;25(8):1358-65
references: 20659224
references: Surg Obes Relat Dis. 2008 May-Jun;4(3):441-4
references: 18065289
references: Arch Surg. 2008 Mar;143(3):235-40; discussion 241
references: 18347269
references: Obes Surg. 2009 May;19(5):577-82
references: 19018603
references: J Cell Sci. 2008 Oct 15;121(Pt 20):3413-21
references: 18827011
references: J Clin Endocrinol Metab. 2011 Oct;96(10):E1630-3
references: 21832118
references: Arch Surg. 2008 Sep;143(9):877-883; discussion 884
references: 18794426
references: Int J Obes (Lond). 2011 Sep;35 Suppl 3:S16-21
references: 21912381
references: Surg Endosc. 2006 Jun;20(6):864-7
references: 16738971
references: Pharmacogenomics. 2006 Sep;7(6):863-87
references: 16981847
references: Trends Endocrinol Metab. 2010 Oct;21(10):610-8
references: 20663687
references: Int J Obes Relat Metab Disord. 2000 Aug;24(8):1051-7
references: 10951545
references: Obes Res. 1994 Sep;2(5):400-10
references: 16358397
references: Nature. 2010 Feb 4;463(7281):666-70
references: 19966786
references: Am J Physiol Endocrinol Metab. 2008 May;294(5):E910-7
references: 18334611
references: Obesity (Silver Spring). 2011 Aug;19(8):1676-83
references: 21311511