Here’s to your health, all 13 parts of it

 

In general how would you rate your overall health?

Excellent/Good/Fair/Poor/Do not know/Prefer not to answer ?

Self rated health is not a measure I would rate very highly, since it would seem to enfold both the ill and the hypochondriacal in a wetly amorous embrace, leading to nosological confusion. Surely it must be better to take your pulse, blood pressure, and do a full diagnostic workup rather than give any credence to fallible self-observation?

On the contrary, this very general question has extraordinary power. Better Self Rated Health showed positive genetic correlations with intelligence (rg = 0.40), education (rg = 0.59), longevity (rg = 0.33), anorexia nervosa (rg = 0.11), and forced expiratory volume in one second (FEV1) (rg = 0.29). Negative genetic correlations were found between better SRH and neuroticism (rg = -0.38), BMI (rg = -0.41), ADHD (rg = -0.38), major depressive disorder (rg = -0.46), schizophrenia (rg = -0.17), systolic and diastolic blood pressure (rg -0.14 and -0.16), coronary artery disease (rg = -0.33), ischaemic stroke (rg = -0.21), and type 2 diabetes (rg= - 0.38). No associations were found for Alzheimer’s disease, bipolar disorder or the ischaemic stroke subtypes.

How do we know this?

Molecular genetic contributions to self-rated health. bioRxiv preprint first posted online October 20, 2015; doi: http://dx.doi.org/10.1101/029504;

Sarah E Harris, Saskia P Hagenaars, Gail Davies, W David Hill, David CM Liewald, Stuart J Ritchie, Riccardo E Marioni, METASTROKE consortium, International Consortium for Blood Pressure, CHARGE consortium Aging and Longevity Group, CHARGE consortium Cognitive Group, Cathie LM Sudlow, Joanna M Wardlaw, Andrew M McIntosh, Catharine R Gale, Ian J Deary.

http://biorxiv.org/content/biorxiv/early/2015/10/20/029504.full.pdf

The Edinburgh gang and their far-flung confederates have crunched the data from UK Biobank in which roughly 500 000 individuals aged between 37 and 73 years were recruited in the United Kingdom between 2006 and 2010. They underwent testing of cognitive abilities, physical and mental health examinations, completed questionnaires about lifestyle, socio-demographic background and family medical history, and agreed to have their health followed longitudinally. For the present study, genome-wide genotyping data were available for 112 151 individuals (58 914 females, 53 237 males) aged 40 to 73 years (mean = 56.91 years, SD = 7.93).

Neuroticism was measured with  12 questions of the Eysenck Personality Questionnaire-Revised Short Form (EPQ-R Short Form). Intelligence was measured by a thirteen item-test with a time limit of two minutes, completed by 36 035 individuals. Six items were verbal and seven numerical. An example of a verbal question is ‘Bud is to flower as child is to?’ Possible answers: 

‘Grow/Develop/Improve/Adult/Old/Do not know/Prefer not to answer

An example of a numerical question is ‘If sixty is more than half of seventy-five, multiply twenty-three by three. If not subtract 15 from eighty-five. Is the answer:

Possible answers: ‘68/69/70/71/72/Do not know/Prefer not to answer

The Intelligence score was the total score out of thirteen. The Cronbach α coefficient for the thirteen items was 0.62 which is reasonable, given that the whole thing takes no more than 120 seconds. And yes, it uses paper and pencil.

Then they crunch all the slushy stuff that is the very code of life, in various ways, but I will stick to the summary of the genome wide analysis. The GWAS identified 13 independent signals associated with SRH, including several in regions previously associated with diseases or disease-related traits. The proportion of variance in SRH that was explained by all common genetic variants was 13%. Polygenic scores for the following traits and disorders were associated with SRH: cognitive ability, education, neuroticism, BMI, longevity, ADHD, major depressive disorder, schizophrenia, lung function, blood pressure, coronary artery disease, large vessel disease stroke, and type 2 diabetes.  In summary: Genetic variants associated with common diseases and psychological traits are associated with self-rated health. The SNP-based heritability of self-rated health is 0.13 (SE 0.006). There is pleiotropy between self-rated health and psychiatric and physical diseases and psychological traits.

Here is the cracker finding: This study shows that the SRH measure, consisting of only one question, is able to reflect the genetic variants of traits and disorders, such as intelligence, personality, cardio-metabolic disease and psychiatric disorders, associated with actual health. Genetic variants associated with higher levels of intelligence and lower levels of cardio metabolic diseases are associated with better health ratings. This supports the theoretical construct of bodily system integrity, a latent trait indicating individual differences in encountering health and cognitive challenges from the environment. Individuals with better system integrity are likely to have higher levels of intelligence, fewer diseases, a better overall health and greater longevity.

The paper is worth reading in detail to get the full argument, and discussions on particular matters like the positive link with anorexia nervosa. System integrity, which Deary named as an afterthought, turns out to be a very powerful concept, increasingly well supported by genetic research. A strength of this study is the large sample size of UK Biobank, permitting powerful and robust tests of pleiotropy between SRH and many health related traits. Other strengths include that all individuals were of white British ancestry, minimising population stratification.

[Note to new readers: Current de facto practice is to avoid genetic group comparisons, despite it being a potential source of understanding genetic effects. However, since genetic groups differ, putting them all into a study can confuse the result. This is one case where apartheid is encouraged, and whites are studied separately.]

The authors end by saying: Measuring people’s overall health is difficult, because the state of the body and mind can be disrupted in many ways, and people’s perceptions of the same objective bodily state can differ. Notwithstanding this complexity, the responses to a single subjective question about whether a person is in good or poor health has proved valid and useful in health research. The present study has been able to identify many genetic contributions to SRH, confirming the complexity of the contributions to the phenotype, and also its partial foundations in genetic differences. The single subjective item of SRH picks up the contributions from many background systems, including mental and physical health, as well as cognitive abilities and personality.

One little question, one very big result.