Play the (genetic) hand you’ve been dealt but don’t spindle, fold or mutilate your cards

Back in the day, computers were programmed by inserting multiple punch cards https://en.wikipedia.org/wiki/Punched_card, each containing a machine instruction. At the bottom of the card it said “do not fold, spindle, or mutilate”. My wife used them back then when she expected to be a widow if and when I got sent to Vietnam.

So it is with you and the genetic hand of coronary artery disease risk you’ve been dealt. [ Cell vol. 167 p. 1431 ’16 ] refers to a recent New England Journal of Medicine article –2016;DOI:http://dx.doi.org/10.1056/NEJMoa1605086.

It’s a very good study, with large numbers of participants in three prospective cohorts — 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) — plus 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. Adherence to a healthy lifestyle among the participants was also determined using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet (hardly complicated).

As you probably know, Genome Wide Association Studies have identified over 50 places in our genomes in which slight variations (the technical term is single nucleotide polymorphisms — SNPs ) are associated with increased risk of coronary artery disease. Since vascular disease is a generalized problem, these SNPs also increase the risk of other vascular problems, notably stroke. None of them increases the risk very much, and even together they don’t explain much of the genetic risk of vascular disease (which we know is there). However, they were all determined (at least in the 4260) and a genetic risk score was calculated. So there were people with high, low and medium degrees of risk.

In all risk groups, high, low, whatever, a simple healthy lifestyle (no smoking, not fat, some exercise, healthy diet) decreased the coronary event rate (heart attack, death) by nearly half. So how bad was high risk? Bad indeed, the event rate in the high risk group was nearly twice that of the low risk group.

Even better, healthy lifestyle decreased risk the most just where you’d want it — in the highest risk group. You can reduce your risk of being eaten by a bear by not going to Yellowstone by 99% or more but so what.

This work is to be believed, because the number of events is high enough –1230 coronary events were observed in the ARIC cohort (median follow-up, 18.8 years), 971 coronary events in the WGHS cohort (median follow-up, 20.5 years), and 2902 coronary events in the MDCS cohort (median follow-up, 19.4 years).

So as my late father said (who lived to 100) when asked what his secret was “I chose my parents very carefully”. Well, we can’t do that, but don’t spindle the cards.

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Comments

  • neil  On December 1, 2016 at 9:52 pm

    Thanks, Friday reading for me in NZ.

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