Haja N. Kadarmideen

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

Abstract This study provides estimates of genetic parameters for various diseases, fertility and 305-day milk production traits in dairy cattle using data from a UK national milk recording scheme. The data set consisted of 63891 multiple lactation records on diseases (mastitis, lameness, milk fever, ketosis and tetany), fertility traits (calving interval, conception to first service, number of services for a conception, and number of days to first service), dystocia and 305-day milk, fat and protein yield. All traits were analysed by multi-trait repeatability linear animal models (LM). Binary diseases and fertility traits were further analysed by threshold sire models (TM). Both LM and TM analyses were based on the generalized linear mixed model framework. The LM included herd-year-season of calving (HYS), age at calving and parity as fixed effects and genetic, permanent environmental and residual effects as random. The TM analyses included the same effects as for LM, but HYS effects were treated as random to avoid convergence problems when HYS sub-classes had 0 or 100% incidence. Because HYS effects were treated as random, herd effects were fitted as fixed effects to account for effect of herds in the data. The LM estimates of heritability ranged from 0•389 to 0•399 for 305-day milk production traits, 0•010 to 0•029 for fertility traits and 0•004 to 0•038 for diseases. The LM estimates of repeatability ranged from 0•556 to 0•586 for 305-day milk production traits, 0•029 to 0•086 for fertility traits and 0•004 to 0•100 for diseases. The TM estimates of heritabilities and repeatabilities were greater than LM estimates for binary traits and were in the range 0•012 to 0•126 and 0•013 to 0•168, respectively. Genetic correlations between milk production traits and fertility and diseases were all unfavorable: they ranged from 0•07 to 0•37 for milk production and diseases, 0•31 to 0•54 for milk production and poor fertility and 0•06 to 0•41 for diseases and poor fertility. These results show that future selection programmes should include disease and fertility for genetic improvement of health and reproduction and for sustained economic growth in the dairy cattle industry.

In the past years, there has been a remarkable development of high-throughput omics (HTO) technologies such as genomics, epigenomics, transcriptomics, proteomics and metabolomics across all facets of biology. This has spearheaded the progress of the systems biology era, including applications on animal production and health traits. However, notwithstanding these new HTO technologies, there remains an emerging challenge in data analysis. On the one hand, different HTO technologies judged on their own merit are appropriate for the identification of disease-causing genes, biomarkers for prevention and drug targets for the treatment of diseases and for individualized genomic predictions of performance or disease risks. On the other hand, integration of multi-omic data and joint modelling and analyses are very powerful and accurate to understand the systems biology of healthy and sustainable production of animals. We present an overview of current and emerging HTO technologies each with a focus on their applications in animal and veterinary sciences before introducing an integrative systems genomics framework for analysing and integrating multi-omic data towards improved animal production, health and welfare. We conclude that there are big challenges in multi-omic data integration, modelling and systems-level analyses, particularly with the fast emerging HTO technologies. We highlight existing and emerging systems genomics approaches and discuss how they contribute to our understanding of the biology of complex traits or diseases and holistic improvement of production performance, disease resistance and welfare.

BACKGROUND: The selection of beef cattle for feed efficiency (FE) traits is very important not only for productive and economic efficiency but also for reduced environmental impact of livestock. Considering that FE is multifactorial and expensive to measure, the aim of this study was to identify biological functions and regulatory genes associated with this phenotype. RESULTS: Eight genes were differentially expressed between high and low feed efficient animals (HFE and LFE, respectively). Co-expression analyses identified 34 gene modules of which 4 were strongly associated with FE traits. They were mainly enriched for inflammatory response or inflammation-related terms. We also identified 463 differentially co-expressed genes which were functionally enriched for immune response and lipid metabolism. A total of 8 key regulators of gene expression profiles affecting FE were found. The LFE animals had higher feed intake and increased subcutaneous and visceral fat deposition. In addition, LFE animals showed higher levels of serum cholesterol and liver injury biomarker GGT. Histopathology of the liver showed higher percentage of periportal inflammation with mononuclear infiltrate. CONCLUSION: Liver transcriptomic network analysis coupled with other results demonstrated that LFE animals present altered lipid metabolism and increased hepatic periportal lesions associated with an inflammatory response composed mainly by mononuclear cells. We are now focusing to identify the causes of increased liver lesions in LFE animals.