Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after Roux-en-Y gastric bypass surgery

Erica S. Rinella, Christopher Still, Yongzhao Shao, G. Craig Wood, Xin Chu, Brenda Salerno, Glenn S. Gerhard, Harry Ostrer

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Context: 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. Design: We conducted a genome-wide association study using a 2-stage phenotypic extreme study design. Setting: Patients were recruited from a comprehensive weight loss program at an integrated health system. Patients: Eighty-six obese (body mass index >35 kg/m2) 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. Intervention: We performed RYGB surgery. Main Outcome Measures: 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 χ2 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.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Gastric Bypass
Polymorphism
Surgery
Single Nucleotide Polymorphism
Weight Loss
Nucleotides
Genes
Genome
Genome-Wide Association Study
Obesity
Weight Reduction Programs
Linear Models
Linear regression
Body Mass Index
Body Weight
Outcome Assessment (Health Care)
Health

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after Roux-en-Y gastric bypass surgery. / Rinella, Erica S.; Still, Christopher; Shao, Yongzhao; Wood, G. Craig; Chu, Xin; Salerno, Brenda; Gerhard, Glenn S.; Ostrer, Harry.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 6, 06.2013.

Research output: Contribution to journalArticle

Rinella, Erica S. ; Still, Christopher ; Shao, Yongzhao ; Wood, G. Craig ; Chu, Xin ; Salerno, Brenda ; Gerhard, Glenn S. ; Ostrer, Harry. / Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after Roux-en-Y gastric bypass surgery. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 6.
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