GWAS of 165,084 Japanese individuals identified nine loci associated with dietary habits

Dietary habits are important factors in our lifestyle, and confer both susceptibility to and protection from a variety of human diseases. We performed genome-wide association studies for 13 dietary habits including consumption of alcohol (ever versus never drinkers and drinks per week), beverages (coffee, green tea and milk) and foods (yoghurt, cheese, natto, tofu, fish, small whole fish, vegetables and meat) in Japanese individuals ( n  = 58,610–165,084) collected by BioBank Japan, the nationwide hospital-based genome cohort. Significant associations were found in nine genetic loci ( MCL1-ENSA , GCKR , AGR3-AHR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , CYP1A2-CSK and ADORA2A-AS1 ) for 13 dietary traits ( P   <  3.8 × 10 −9 ). Of these, ten associations between five loci and eight traits were new findings. Furthermore, a phenome-wide association study revealed that five of the dietary trait-associated loci have pleiotropic effects on multiple human complex diseases and clinical measurements. Our findings provide new insight into the genetics of habitual consumption. Matoba et al. performed GWAS on 13 dietary habits in Japanese individuals, identifying ten new associations in eight traits and five dietary-trait-associated loci with pleiotropic effects on multiple human disease and clinical measurements.

[1]  E. Rimm,et al.  Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption , 2011, PLoS genetics.

[2]  M. Kubo,et al.  A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study , 2018, Scientific Reports.

[3]  M. Kanai,et al.  GWAS of smoking behaviour in 165,436 Japanese people reveals seven new loci and shared genetic architecture , 2019, Nature Human Behaviour.

[4]  A. Tremblay,et al.  Yogurt, diet quality and lifestyle factors , 2017, European Journal of Clinical Nutrition.

[5]  T. Ogihara,et al.  Confirmation of ALDH2 as a Major locus of drinking behavior and of its variants regulating multiple metabolic phenotypes in a Japanese population. , 2011, Circulation Journal.

[6]  Marcia M. Nizzari,et al.  Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels , 2007, Science.

[7]  Xueli Yang,et al.  Common variants at 12q24 are associated with drinking behavior in Han Chinese. , 2013, The American journal of clinical nutrition.

[8]  Sanghoon Moon,et al.  Evaluation of pleiotropic effects among common genetic loci identified for cardio-metabolic traits in a Korean population , 2016, Cardiovascular Diabetology.

[9]  M. Kubo,et al.  ALDH2 polymorphism is associated with fasting blood glucose through alcohol consumption in Japanese men , 2016, Nagoya journal of medical science.

[10]  R. Mägi,et al.  Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption. , 2011, Human molecular genetics.

[11]  Y. Kamatani,et al.  Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population , 2019, European Journal of Human Genetics.

[12]  A. Turrini,et al.  Sociodemographic and lifestyle characteristics of yogurt consumers in Italy: Results from the INRAN-SCAI 2005-06 survey , 2015 .

[13]  Ahmed El-Sohemy,et al.  Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. , 2007, The American journal of clinical nutrition.

[14]  Kazuhiko Yamamoto,et al.  Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese , 2018, Nature Communications.

[15]  M. Daly,et al.  An Atlas of Genetic Correlations across Human Diseases and Traits , 2015, Nature Genetics.

[16]  L A Farrer,et al.  Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci , 2014, Molecular Psychiatry.

[17]  I. Deary,et al.  Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117) , 2017, Molecular Psychiatry.

[18]  S. Katsuura-Kamano,et al.  Inverse association between soy food consumption, especially fermented soy products intake and soy isoflavone, and arterial stiffness in Japanese men , 2018, Scientific Reports.

[19]  Yakir A Reshef,et al.  Partitioning heritability by functional annotation using genome-wide association summary statistics , 2015, Nature Genetics.

[20]  B. Voight,et al.  Patterns of shared signatures of recent positive selection across human populations , 2017, Nature Ecology & Evolution.

[21]  P. Kraft,et al.  A genome-wide association study of energy intake and expenditure , 2018, PloS one.

[22]  Y. Okada.  eLD: entropy-based linkage disequilibrium index between multiallelic sites , 2018, Human Genome Variation.

[23]  M. Inoue,et al.  Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. , 2005, Journal of the National Cancer Institute.

[24]  M. Kanai,et al.  Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population , 2019, Nature Genetics.

[25]  T. Hansen,et al.  Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[26]  K. Rawlik,et al.  An atlas of genetic associations in UK Biobank , 2017, Nature Genetics.

[27]  D. Chasman,et al.  A genome-wide association study of bitter and sweet beverage consumption. , 2019, Human molecular genetics.

[28]  W. Daniel,et al.  Effect of cytochrome P450 (CYP) inducers on caffeine metabolism in the rat. , 2007, Pharmacological reports : PR.

[29]  M. Daly,et al.  LD Score regression distinguishes confounding from polygenicity in genome-wide association studies , 2014, Nature Genetics.

[30]  J. J. Wang,et al.  Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption , 2014, Molecular Psychiatry.

[31]  Dajiang J. Liu,et al.  Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use , 2018, Nature Genetics.

[32]  Y. Kamatani,et al.  Overview of the BioBank Japan Project: Study design and profile , 2017, Journal of epidemiology.

[33]  I. Deary,et al.  Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N= 112117) , 2017 .

[34]  Audrey Y. Chu,et al.  Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts , 2017, PloS one.

[35]  M. Schwab,et al.  Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. , 2013, Pharmacology & therapeutics.

[36]  M. Suganuma,et al.  Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention. , 2000, BioFactors.

[37]  M. Kanai,et al.  Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases , 2018, Nature Genetics.

[38]  T. Spector,et al.  Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior. , 2016, Human molecular genetics.

[39]  B. Han,et al.  Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men. , 2011, The American journal of clinical nutrition.

[40]  A. Linneberg,et al.  The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors. , 2008, Alcoholism, clinical and experimental research.

[41]  L. Karssen,et al.  Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption , 2016, Scientific Reports.

[42]  Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM , 2011, Molecular Psychiatry.

[43]  N. Risch,et al.  Genetic Contributors to Variation in Alcohol Consumption Vary by Race/Ethnicity in a Large Multi-Ethnic Genome-wide Association Study , 2017, Molecular Psychiatry.

[44]  Daniel Marbach,et al.  Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics , 2016, PLoS Comput. Biol..

[45]  M. Kanai,et al.  Genome-wide association study identifies 112 new loci for body mass index in the Japanese population , 2017, Nature Genetics.

[46]  A. McQuillin,et al.  Genetic variants in ALDH1B1 and alcohol dependence risk in a British and Irish population: A bioinformatic and genetic study , 2017, PloS one.

[47]  S. Tsugane,et al.  The JPHC study: design and some findings on the typical Japanese diet. , 2014, Japanese journal of clinical oncology.

[48]  A. Guillouzo,et al.  Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes. , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[49]  P. O’Reilly,et al.  KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference , 2016, Proceedings of the National Academy of Sciences.

[50]  Ellen T. Gelfand,et al.  The Genotype-Tissue Expression (GTEx) project , 2013, Nature Genetics.