Key findings

alcohol consumption

The effect of alcohol consumption on mortality was examined in participants without chronic disease at baseline. When compared with those that drank alcohol less than once a month, those that drank the equivalent of 500 ml of spirits or more a week had a 43% higher all-cause mortality, and nearly 3 times the mortality from alcohol-related diseases. Overall, higher alcohol consumption, episodic drinking, and very high percentage alcoholic products were all associated with increased mortality. Read full paper and press release.

cognitive impairment

Cognitive impairment was measured in 9,299 participants aged 50-89 using the Mini Mental State Examination. Twenty-four percent of this population had cognitive impairment and this ranged from 10% in those aged 50-59 to 55% in those aged 80-89. The prevalence of cognitive impairment was higher in women than in men. There was little difference in the prevalence of cognitive impairment between participants with or without diabetes, hypertension, overweight or obesity (Body Mass Index [BMI] ≥ 25 km/m²), or high levels of fat mass. Read full paper.

DIABETES

At recruitment, nearly half of women and one-third of men aged 50-59 were living with obesity (BMI ≥30 kg/m²). By age 60, more than one in five participants had a confirmed diagnosis of diabetes.

Adults with diabetes had four times the overall death rate between ages 35-74 compared with those without diabetes. The excess mortality accounted for at least one-third of all deaths in this age range – about twice the proportion suggested by previous studies. Read full paper.

The highest excess risk of death among people with diabetes was due to kidney disease, followed by heart and other vascular disease, infection and acute diabetic crises. Subsequent Mendelian Randomisation studies confirmed that these associations were causal, with larger effect estimates than previously observed in European and East Asian populations. Read full paper. Further analyses have also revealed the types of infection most strongly related to diabetes. Read full paper.

OBESITY

Obesity makes diabetes and several other chronic diseases more common but these diseases can cause substantial weight loss hiding their initial cause. To address this, we examined the association between obesity and mortality more than five years after recruitment, excluding participants with chronic disease at baseline.

We found that both general obesity and excess abdominal fat were major risk factors for premature death. Among individuals with a BMI above 25 kg/m², each increase of 5 kg/m² was associated with a 30% higher risk of death. Waist circumference showed an especially strong association with mortality, highlighting the particular harm of abdominal obesity. Read full paper.

We also conducted Mendelian Randomisation analyses to assess the lifelong effects of obesity on mortality (including those driven through diabetes). In participants aged 35–74 years, a 5 kg/m² higher genetically predicted BMI was associated with nearly double the risk of death from any cause, with the largest effects seen for vascular–metabolic diseases and infections. At least half of the excess mortality risk from higher BMI was attributable to its effect on diabetes. Read full paper.

By measuring nuclear magnetic resonance (NMR) blood biomarkers we found positive associations between both higher total fat and higher abdominal fat with numerous molecules in the blood that are linked to type 2 diabetes and heart disease. Conversely, higher hip and upper thigh fat were associated with a favourable NMR metabolic profile. Read full paper.

BMI is the sum of Fat Mass Index (FMI) and Lean Mass Index (LMI). We found that FMI and LMI had independent but opposite associations with death from vascular and metabolic causes. This suggests that using BMI alone to assess disease risk may be less informative than using FMI and LMI. Read full paper.

BMI was strongly associated with death due to COVID-19 in 2020. However, even in 2020 other causes of death accounted for more than twice as many deaths as COVID-19, so the absolute effect of BMI on mortality was still greater for the aggregate of those other causes than for COVID-19. Read full paper.

SMOKING AND CAUSE-SPECIFIC MORTALITY

Smoking a few cigarettes a day – ‘low intensity smoking’ - was associated with increased mortality, particularly from respiratory cancers, chronic obstructive pulmonary disease and gastrointestinal and vascular diseases. Of those smoking an average of about 10 cigarettes per day, about one third were killed by their habit. However, as in other populations, quitting substantially reduced these risks. Read full paper.

BLOOD PRESSURE

Observational analyses demonstrated that blood pressure was a major risk factor for death from a range of diseases. This strong association was especially related to death from vascular and kidney disease, with no ‘threshold’ levels below which lower blood pressure was not associated with lower risk. As those with diabetes were at substantially higher risk than those without diabetes, the mortality rates associated with elevated blood pressure were much higher in these individuals. Read full paper. Further analyses using Mendelian Randomisation reinforced the association of blood pressure with death from cardiovascular disease and of high systolic blood pressure with death from kidney disease. Read full paper.

SOCIOECONOMIC STATUS

Participants with no formal education had about twice the mortality rate of participants with tertiary level education, resulting in an average reduction in life expectancy of approximately six years. Lifestyle factors such as smoking, alcohol drinking, and leisure time physical activity and the related physiological correlates of obesity, diabetes, and high blood pressure accounted for about four-fifths of the association of education with premature death. Read full paper.

GENETIC ANALYSES

People with Latino ethnic background are under represented in genetic research. Through an academic-industry partnership with the Regeneron Genetics Center® and AstraZeneca we generated genotype and exome data for the whole cohort, and whole-genome sequencing data for a subset of 9,950 participants. This is one of the most extensive sequencing studies of individuals from non-European ancestry and a major step forward for diversity in genetic research. Read full paper and press release.

These data have already contributed to several new discoveries, including:

Combining MCPS data with data from a further 500,000 people in the UK and the US led to the discovery of rare genetic variations in the GPR75 gene that were associated with protection against obesity. Read full paper and press release.
Variants in the MAP3K15 gene were shown to protect against diabetes. The protective effect was stronger in individuals who did not carry the Latino-enriched SLC16A11 risk haplotype. Read full paper.
Truncations of the gene INHBE were associated with favourable fat distribution, favourable metabolic profile and protection from diabetes. Read full paper.
Rare loss-of-function mutations in the CHRNB2 gene were associated with a reduced likelihood of heavy smoking. Read full paper.
Protein-truncating variants in BSN were associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease. Read full paper.
Meta-analyses of MCPS and UK Biobank data identified five novel loci associated with clonal haematopoiesis. Read full paper.
Identification of several variants associated with reduced prostate cancer risk and severity. The analysis also confirmed some previously identified variants associated with increased risk. Read full paper.

MCPS genetic data has contributed to the RGC Million Exome Variant Browser dataset which is derived from 983,578 exomes and provides a harmonized catalogue of around 20 million coding variants in individuals from a diverse array of ancestries. It is an invaluable resource for interpreting rare variants and is a big step towards precision medicine. Read full paper.

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