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Autoimmune diseases are a major challenge for global health. From an evolutionary biology perspective, reproduction, particularly androgens, trades off against immune activity.1 Correspondingly, trials suggest androgens improve rheumatoid arthritis (RA).2 3 As such, dietary factors promoting reproduction might prevent or treat autoimmune disorders. Linoleic acid (LA) is a major n−6 polyunsaturated fatty acid (PUFA) in widely used polyunsaturated vegetable oils, such as sunflower, corn, soybean and cottonseed oil. In animal experiments, LA stimulates the synthesis of testosterone.4 Observationally, endogenous LA is inversely associated with RA5 and systemic lupus erythematosus (SLE),6 but these findings have not been confirmed in randomised controlled trials. Comparing autoimmune disorders according to naturally occurring LA-related genetic variants, that is, Mendelian randomisation (MR), provides a means of obtaining unconfounded estimates of causal effects. We obtained strong, independent genetic predictors of LA using (1) the three most significant uncorrelated single-nucleotide polymorphisms (SNPs) and (2) …

BackgroundAdiposity is associated with asthma although studies do not usually explore the inter-related role of childhood and adult adiposity in asthma risk using a life course perspective.MethodsWe conducted a Mendelian randomisation (MR) study using genetic instruments for childhood body mass index (BMI) (n=47 541), childhood obesity (n=29 822) and adult BMI (n=681 725) applied to the UK Biobank (n=401 837), with validation in a genome-wide association study of asthma (GABRIEL, n=5616). We used inverse variance weighting and other sensitivity analyses to examine the relationship between adiposity and asthma risk. We assessed mediation using multivariable Mendelian randomisation (MVMR) analysis.ResultsChildhood BMI was related to asthma in the UK Biobank (OR 1.10 per SD increase, 95% CI 0.99 to 1.22). Adult BMI was associated with asthma risk (OR 1.33 per SD increase, 95% CI 1.25 to 1.43). Analyses in GABRIEL gave directionally consistent results but with wide CI. The relationship between childhood obesity and asthma risk was less clear in both data sources. MVMR suggested the relation of childhood BMI with asthma risk was largely mediated via adult BMI.ConclusionAdiposity in childhood likely cause asthma, but the effect is primarily mediated via adult BMI.

We are pleased that our article on the role of linoleic acid (LA) in autoimmune disorders is of interest to readers. However, regarding the methodological issues raised by Lee,1 several points need to be considered and clarified. First, Mendelian randomisation (MR) requires stringent assumptions, that is, the genetic instruments are associated with the exposure, are not linked with the outcomes other than via effects on the exposure and no confounders of the associations of the genetic instruments with the outcome exist.2 We agree that weak instruments which violate these assumptions would lead to biased associations. As such, we are very cautious in the selection of genetic instruments. Specifically, we used the most significant three uncorrelated (r2

In observational studies of Western populations, moderate alcohol use is usually associated with lower cancer mortality rates. However, moderate alcohol use (regular drinking of moderate amounts) is socially patterned. Evidence from other contexts can clarify such observations. We examined the association of moderate alcohol use with death from cancer in older Chinese adults from a developed non-Western setting, where occasional alcohol drinking (less than once per week of small amounts) is typical.Multivariable Cox regression analysis was used to assess the adjusted associations of alcohol use with death from cancer using a population-based prospective cohort of 66 820 Chinese aged ≥ 65 years enrolled from July 1998 to December 2001 at all the 18 Elderly Health Centres of the Hong Kong Government Department of Health, and followed till 30 May 2012.After follow-up for about 10.5 years, 6335 cancer deaths were identified. Most current alcohol users were social drinkers (1/week). Moderate drinkers had a similar risk of death from non-oesophageal cancer as never drinkers, but a higher risk of oesophageal cancer, adjusted for age, sex, socioeconomic position, lifestyle and health status. Social drinking (1/week) was associated with a lower risk of death from non-oesophageal cancer, but not from oesophageal cancer.In a non-Western setting, no association of moderate alcohol use with death from cancer was found. Occasional social drinking (1/week) was associated with a lower risk of cancer, suggesting that moderate alcohol use is not protective, but in any setting the attributes of being a typical drinker may be.

Background Childhood adiposity in developed countries is often associated with lower socio-economic position (SEP) of the family and neighbourhood. However, the association of adiposity with SEP varies with national income. The authors examined whether childhood BMI was associated with family or neighbourhood socio-economic characteristics in a recently and rapidly developed Chinese population. Methods The authors used multilevel modelling in Hong Kong9s population-representative ‘Children of 1997’ birth cohort (n=8327) to examine the association of BMI z-score and overweight (including obesity) at ages 6–11 years with parental education, mother9s birthplace, sex and neighbourhood median income. Results In 7108 (85 % successful follow-up) children, boys were more adipose than girls. The association of parental education with BMI z-score varied with mother9s birthplace (p value for interaction 0.001). In children of Hong Kong-born mothers, parental education was negatively associated with BMI z-score (mean difference –0.15, 95% CI –0.25 to –0.05 for highest compared with lowest). However, in children of mainland China-born mothers, parental education was positively associated with BMI z-score (0.18, 95% CI 0.02 to 0.34 in the same comparison). Neighbourhood had no association with BMI z-score. Conclusions In this recently developed Chinese population, there was no consistent association between socio-economic characteristics and childhood BMI. Other factors, such as experience of economic transition, as proxied by mother9s place of birth, exerted a modifying impact. The cultural and biological mechanisms underlying these socio-historical intergenerational influences need to be determined, so that effective interventions can be implemented in China and elsewhere.

Background Research on trends in cancer incidence has usually examined single sites in populations that long ago completed the economic transition. The trends in 11 cancers in three groups in the recently transitioned Hong Kong Chinese population were examined to delineate the effects of economic transition and provide generalised aetiological insights. Methods Sex-specific Poisson models were fitted to cancer incidence in Hong Kong (1974–2003) to examine age, period and birth cohort effects. Cancers were grouped as: hormonally modulated (including breast, endometrium, ovary and prostate), infection-related (cervix, liver, nasopharynx, lymphoma and stomach) and lifestyle-related (colorectum and lung). Results Age-standardised incidence of hormonally modulated female cancers increased for the first generation (women born ∼1940) to experience puberty in the transitioning environment of Hong Kong. Prostate cancer incidence increased, despite a downturn for the first generation growing up in Hong Kong. Incidence of infection-related cancers decreased, mainly due to birth cohort effects; coinciding with birth for liver cancer and lymphoma, with reaching adulthood for cervical and male nasopharyngeal cancers, and with a generation for stomach cancer. Lifestyle-related cancers had sex-specific declines by birth cohort. Conclusion With economic transition and the associated lifestyle changes, environmentally determined levels of pubertal female hormones may drive intergenerational increases in hormonally related female cancers. Economic development, via improved living conditions, may also reduce infection-related cancers, possibly including prostate cancer; however, the effects depend on transmission dynamics and perhaps specific public health initiatives. In traditional societies, males may benefit from economic development sooner than females.

Jahangir et al 1 provided a fascinating analysis showing, among older people, a higher risk of abdominal aortic aneurysm (AAA) in those with normal body mass index (BMI), those who smoke and in men. Although AAA is relatively rare, ruptured AAA has a high mortality rate, so prevention, based on reversible risk factors, is important. The observed association of normal BMI with AAA may be an artefact of weight loss due to ill-health in older people. Men often have higher rates than women of cardiovascular disease, for reasons …

Genetic studies could help us interpret a biologically plausible but preliminary association