Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

TY - JOUR

T1 - Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

AU - LOLIPOP study

AU - Justice, Anne E

AU - Winkler, Thomas W

AU - Feitosa, Mary F

AU - Graff, Misa

AU - Fisher, Virginia A

AU - Young, Kristin

AU - Barata, Llilda

AU - Deng, Xuan

AU - Czajkowski, Jacek

AU - Hadley, David

AU - Ngwa, Julius S

AU - Ahluwalia, Tarunveer S

AU - Chu, Audrey Y

AU - Heard-Costa, Nancy L

AU - Lim, Elise

AU - Perez, Jeremiah

AU - Eicher, John D

AU - Kutalik, Zoltán

AU - Xue, Luting

AU - Mahajan, Anubha

AU - Renström, Frida

AU - Wu, Joseph

AU - Qi, Qibin

AU - Ahmad, Shafqat

AU - Alfred, Tamuno

AU - Amin, Najaf

AU - Bielak, Lawrence F

AU - Bonnefond, Amelie

AU - Bragg, Jennifer

AU - Cadby, Gemma

AU - Chittani, Martina

AU - Coggeshall, Scott

AU - Corre, Tanguy

AU - Direk, Nese

AU - Eriksson, Joel

AU - Fischer, Krista

AU - Gorski, Mathias

AU - Neergaard Harder, Marie

AU - Horikoshi, Momoko

AU - Huang, Tao

AU - Huffman, Jennifer E

AU - Jackson, Anne U

AU - Justesen, Johanne Marie

AU - Kanoni, Stavroula

AU - Kinnunen, Leena

AU - Wu, Ying

AU - Afaq, Saima

AU - Wild, Sarah

AU - Zhao, Wei

AU - Wilson, James F

PY - 2017/4/26

Y1 - 2017/4/26

N2 - Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

AB - Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

KW - Adiposity/genetics

KW - Adult

KW - Body Fat Distribution

KW - Body Mass Index

KW - Epistasis, Genetic

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study/methods

KW - Humans

KW - Obesity/genetics

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci/genetics

KW - Smoking/genetics

KW - Waist Circumference/genetics

KW - Waist-Hip Ratio

U2 - 10.1038/ncomms14977

DO - 10.1038/ncomms14977

M3 - Article

C2 - 28443625

SN - 2041-1723

VL - 8

SP - 14977

JO - Nature Communications

JF - Nature Communications

ER -