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Consortium of Researchers Report Novel Loci Linked to Coffee Habit

NEW YORK (GenomeWeb) – Through a genome-wide meta-analysis, an international team of researchers has linked half a dozen novel loci to coffee consumption.

Researchers from the Coffee and Caffeine Genetics Consortium drew on genome-wide data from more than 120,000 coffee drinkers of European and African ancestry. As they reported today in Molecular Psychiatry, two of the loci they uncovered mapped to genes involved in caffeine metabolism while two other loci may be associated with the rewarding effects of java drinking. Additional loci were near genes not previously associated with caffeine metabolism or its neurological effects.

"Coffee and caffeine have been linked to beneficial and adverse health effects. Our findings may allow us to identify subgroups of people most likely to benefit from increasing or decreasing coffee consumption for optimal health," first author Marilyn Cornelis from Harvard School of Public Health said in a statement.

To find loci linked to coffee consumption, Cornelis and her colleagues drew on data from 28 studies of people of European ancestry. They then tested the top hits they uncovered — 44 SNPs from 33 genomic regions — in a further 13 studies of people of European ancestry and in seven studies of people of African ancestry.

Eight loci, including six novel ones, were of genome-wide significance.

These loci, the researchers reported, have effect sizes of 0.03 to 0.14 cups per day per allele and explain some 1.3 percent of phenotypic coffee consumption.

In this study as in previous ones, two loci near AHR and CYP1A2 were the most prominent ones linked to coffee consumption. Two alleles in particular have been linked to increased coffee drinking, but also to lower plasma levels of caffeine. And one of those alleles — the rs4410790 C allele — has been associated with the methylation of AHR in the cerebellum and may, the researchers said, indicate a role for AHR in the motor or learning pathways that lead to coffee drinking.

The other six loci the researchers uncovered hadn't been previously linked to coffee drinking, though four of those loci map to gene regions that hint at possible roles related to coffee metabolism or to the neurologically rewarding effects of drinking coffee.

One loci, for instance, was traced to the 3' UTR of POR, which encodes the oxidoreductase P450 that transfers electrons of microsomal CYP450 enzymes, and is linked to caffeine metabolism. The rs17685 A variant associated with drinking larger amounts of coffee was also linked with increased POR expression, leading the researchers to suspect that the variant may reduce the binding of POR expression inhibitors like BHLHE40.

Meanwhile, the index SNP at 11p13 is a missense mutation in BDNF, which is involved in regulating the activity of neurotransmitters like serotonin, dopamine, and glutamate, which are involved in mood regulation as well as memory and learning. The Met66 allele, the researchers noted, affects the secretion of BDNF and may diminish the rewarding effects of coffee and thus its consumption.

How the additional loci, which map to the GCKR and MLXIPL genes and are involved in glucose traits and plasma triglycerides, respectively, may have an affect coffee consumption is unclear.

Still, the researchers said their study indicates that there are genetic variants associated with a coffee habit.

"Like previous genetic analyses of smoking and alcohol consumption, this research serves as an example of how genetics can influence some types of habitual behavior," senior author Daniel Chasman from Brigham and Women's Hospital added.

Cornelis, Chasman, and their colleagues also pointed out that cultural norms surrounding coffee drinking might have reduced their power for uncovering loci. They were unable, they reported, to replicate these findings in a Pakistani population where coffee drinking is uncommon.