Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

被引：200

作者：

Cornelis, M. C. ^{[1
,2
]}

Byrne, E. M. ^{[3
]}

Esko, T. ^{[4
,5
,6
,7
]}

Nalls, M. A. ^{[8
]}

Ganna, A. ^{[9
]}

Paynter, N. ^{[10
]}

Monda, K. L. ^{[11
]}

Amin, N. ^{[12
]}

Fischer, K. ^{[4
]}

Renstrom, F. ^{[13
]}

Ngwa, J. S. ^{[14
]}

Huikari, V. ^{[15
]}

Cavadino, A. ^{[16
]}

Nolte, I. M. ^{[17
]}

Teumer, A. ^{[18
]}

Yu, K. ^{[19
]}

Marques-Vidal, P. ^{[20
]}

Rawal, R. ^{[21
]}

Manichaikul, A. ^{[22
]}

Wojczynski, M. K. ^{[23
]}

Vink, J. M. ^{[24
]}

Zhao, J. H. ^{[25
]}

Burlutsky, G. ^{[26
,27
]}

Lahti, J. ^{[28
,29
]}

Mikkila, V. ^{[30
,31
,32
]}

Lemaitre, R. N. ^{[33
]}

Eriksson, J. ^{[34
]}

Musani, S. K. ^{[35
]}

Tanaka, T. ^{[36
]}

Geller, F. ^{[37
]}

Luan, J. ^{[25
]}

Hui, J. ^{[38
,39
,40
,41
]}

Maegi, R. ^{[4
]}

Dimitriou, M. ^{[42
]}

Garcia, M. E. ^{[43
]}

Ho, W-K ^{[44
]}

Wright, M. J. ^{[45
]}

Rose, L. M. ^{[10
]}

Magnusson, P. K. E. ^{[9
]}

Pedersen, N. L. ^{[9
]}

Couper, D. ^{[46
]}

Oostra, B. A. ^{[47
]}

Hofman, A. ^{[12
]}

Ikram, M. A. ^{[12
,48
,49
]}

Tiemeier, H. W. ^{[12
,50
]}

Uitterlinden, A. G. ^{[12
,51
]}

van Rooij, F. J. A. ^{[12
]}

Barroso, I. ^{[52
,53
,54
]}

Johansson, I. ^{[55
]}

Xue, L. ^{[14
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02215 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA

[3] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[4] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[5] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA

[6] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA

[7] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[8] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[9] Karolinska Inst, Dept Med Epidemiol & Biostat, Karolinska, Sweden

[10] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA

[11] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[12] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[13] Lund Univ, Dept Clin Sci, Malmo, Sweden

[14] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[15] Univ Oulu, Inst Hlth Sci, Oulu, Finland

[16] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, Ctr Epidemiol Child Hlth,MRC, London, England

[17] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[18] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[19] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[20] Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland

[21] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Munich, Germany

[22] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[23] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA

[24] Vrije Univ Amsterdam, Dept Biol Psychol Netherlands Twin Register, Amsterdam, Netherlands

[25] Univ Cambridge, Epidemiol Unit, MRC, Cambridge, England

[26] Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Sydney, NSW 2006, Australia

[27] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia

[28] Univ Helsinki, Inst Behav Sci, Helsinki, Finland

[29] Folkhalsan Res Ctr, Helsinki, Finland

[30] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland

[31] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland

[32] Turku Univ Hosp, FIN-20520 Turku, Finland

[33] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[34] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden

[35] Univ Mississippi, Med Ctr, Jackson, MI USA

[36] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA

[37] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[38] Busselton Populat Med Res Fdn Inc, Busselton, WA, Australia

[39] PathWest Lab Med, Nedlands, WA, Australia

[40] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia

[41] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia

[42] Harokopio Univ, Athens, Greece

[43] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA

[44] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England

[45] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[46] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[47] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[48] Erasmus MC, Dept Radiol, Rotterdam, Netherlands

[49] Erasmus MC, Dept Neurol, Rotterdam, Netherlands

[50] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands

来源：

MOLECULAR PSYCHIATRY | 2015年 / 20卷 / 05期

关键词：

PROTEIN; CAFFEINE; GLUCOKINASE; INVOLVEMENT; VARIANTS; RECEPTOR; BINDING; BRAIN; BDNF;

D O I：

10.1038/mp.2014.107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in similar to 30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log(10)Bayes factor (BF) > 5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P < 5x10(-8)). Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

引用

页码：647 / 656

页数：10

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