Answer: Try drinking coffee–and hope you are one of the lucky 25% of the population who carry the gene that strongly protects against Parkinson’s in the presence of enough caffeine/coffee.
This is a brilliant scientific paper is worth the hard slog of reading it:
Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson’s disease modifier gene via interaction with coffee.
Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu SA, Scott WK, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H.
PLoS Genet. 2011 Aug;7(8):e1002237.
.
I’ve extracted the key bits:
.
Author plain English summary:
Parkinson’s disease (PD), like most common disorders,
involves interactions between genetic make-up and
environmental exposures that are unique to each individual.
Caffeinated-coffee consumption may protect some
people from developing PD, although not all benefit
equally. In a genome-wide search, we discovered that
variations in the glutamate-receptor gene GRIN2A modulate
the risk of developing PD in heavy coffee drinkers. The
study was hypothesis-free, that is, we cast a net across the
entire genome allowing statistical significance to point us
to a genetic variant, regardless of whether it fell in a
genomic desert or an important gene. Fortuitously, the
most significant finding was in a well-known gene, GRIN2A,
which regulates brain signals that control movement and
behavior. Our finding is important for three reasons: First,
it is a proof of concept that studying genes and
environment on the whole-genome scale is feasible, and
this approach can identify important genes that are missed
when environmental exposures are ignored. Second, the
knowledge of interaction between GRIN2A, which is
involved in neurotransmission in the brain, and caffeine,
which is an adenosine-A2A-receptor antagonist, will
stimulate new research towards understanding the cause
and progression of PD. Third, the results may lead to
personalized prevention of and treatment for PD.
Parkinson’s disease is becoming more common as our population ages:
PD is the
second most common neurodegenerative disease after Alzheimer’s
disease; it affects about 5 million individuals in the 10 most
populous nations and is expected to double in frequency by 2030
[3]. Until the 1990’s PD was thought to be purely environmental
with no genetic component. In the last decade, numerous genes
have been identified, some of which can cause PD [4] and others
that are susceptibility loci [5–10]. There are also compelling data
from epidemiology that cigarette smoking and caffeinated-coffee
consumption are associated with reduced risk of developing PD
[11,12] and that exposure to environmental neurotoxins is
associated with increased risk of developing PD [13].
If they were lucky to be in the 25% of people with the protective variant of the GRIN 2A gene, heavy coffee drinkers were 59% less likely to get PD than were light/nil coffee drinkers; if they didn’t have the protective variant of the gene, heavy coffee drinkers were 18% less likely to get PD than were light/nil coffee drinkers:
In a genome-wide gene-environment study we identified
GRIN2A as a genetic modifier of the inverse association of coffee
with the risk of developing PD. The discovery was made in
NGRC, and replicated in independent data. Risk reduction by
heavy coffee use, which was estimated to be 27% on average, was
genotype-specific and varied according to GRIN2A genotype from
18% (P= 361023) for individuals with rs4998386_CC genotype to
59% (P= 6610213) for those with rs4998386_TC genotype. When
coffee intake was categorized in four doses, the dose trend was
more prominent in individuals with rs4998386_T allele than those
with rs4998386_CC genotype, with the 3rd and 4th quartiles
exhibiting only 11% and 39% risk reduction for rs4998386_CC
carriers, vs. 37% and 66% for rs4998386_T carriers.
If they didn’t drink coffee, having the protective variant of the gene offered no protection at all:
compared to the light coffee drinkers with
GRIN2A_rs4998386_CC genotype (the group with highest risk),
heavy coffee use (with CC genotype) reduced risk by 18%
(OR = 0.82, P= 361023), having GRIN2A_rs4998386_T allele
(light coffee) had no effect on risk (OR =1.0, P= 0.99), but the
combination of heavy coffee use and GRIN2A_rs4998386_TC
genotype was associated with a highly significant 59% risk
reduction (OR = 0.41, P =6610213)
How much caffeine did the study subjects have to drink each day to be called a heavy user? About 238 mg–that’s about two and a half espresso-type coffees a day:
To classify coffee/caffeine intake, each
dataset was treated separately according to the measurements
available. The median ccy or mg was determined for controls
within each dataset (excluding those with zero intake) and used as
the cut-off for heavy drinkers (.median) vs. light drinkers (0 to
#median). The median was 67.5 ccy for NGRC, 74.0 ccy for
PEG, 70.0 ccy for HIHG, and 237.8 mg/day for PAGE.
