Publications

Selected Recent Research Publications

Evans DM, Moen GH, Hwang L, Lawlor DA, Warrington N (2019). Elucidating the Role of Maternal Environmental Exposures on Offspring Health and Disease Using Two-Sample Mendelian Randomization. Int J Epidemiol. doi: 10.1093/ije/dyz019

This manuscript presents three big ideas in the epidemiological study of mothers and their children: (1) the idea of paritioning genetic effects into a maternal and fetal component to understand the causal effects of maternal factors on their children, and methods for accomplishing this task, (2) two sample Mendelian randomization in (different) studies of mothers and children, (3) the application of these methods to address the Developmental Origins of Health and Disease (DOHAD) showing how maternal SNPs that influence offspring birthweight can be used to proxy intra-uterine growth restriction and hence be used as a test of the hypothesis in genotyped mother-offspring pairs. The paper is also a clarion call for trans-generational GWAS.

Warrington NM, …, Evans DM*, Freathy RM* (2019). Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet, 51(5), 804-814.

This paper illustrates application of many of the ideas articulated in the Evans et al. (2019) paper. We we used Mendelian Randomization to confirm that high maternal blood pressure was causal for decreased offspring birth weight, and used the UK Biobank study to provide preliminary evidence that maternal SNPs associated with lower offspring BW were associated with decreased (NOT increased) offspring blood pressure in later life. This latter result is contradictory to DOHAD theories, which predict that maternal SNPs associated with intrauterine growth restriction should be associated with increased (not decreased) offspring blood pressure and potentially over turning thirty years of epidemiological research.

Warrington NM, Freathy RM, Neale MC, Evans DM (2018). Using structural equation modelling to jointly estimate maternal and fetal effects on birthweight in the UK Biobank. Int J Epidemiol, 47(4), 1229-1241. doi: 10.1093/ije/dyy015.

Kemp JP, …, Richards JB, Evans DM (2017). Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet, 49(10), 1468-1475. (cites = 141)

Zheng J, …, Evans DM*, Neale BM* (2016). LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics, 33(2), 272-279. (cites = 341)

The LDHub software is an online database and utility that users can use to estimate genetic correlations between their trait of interest and other diseases and traits for which there is publicly available GWAS data.

Horikoshi M, …, Evans DM*, McCarthy MI*, Freathy RM*, on behalf of the Early Growth Genetics (EGG) Consortium (2016). Genome-wide associations for birth weight and correlations with adult disease. Nature 538(7624), 248-52. (cites = 203)

We discovered 54 novel genetic variants associated with birth weight and showed that the well-established relationship between low birthweight and increased risk of cardio-metabolic disease in later life was predominantly mediated by genetic factors. Our result contrasts with the preeminent paradigm of the last 30 years (i.e. the Developmental Origins of Health and Disease (DoHaD) Hypothesis first proposed by David Barker) which has postulated that the inverse relationship between birth weight and cardiometabolic risk is due to an adverse in-utero environment and subsequent “foetal programming”. Our result suggests that the DoHaD hypothesis needs to be re-examined in the light of our findings. Our results also have clinical implications for the prenatal care of infants, suggesting that strategies focused on increasing infant birthweight, may not necessarily translate to decreased cardiometabolic risk in later life.