https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48511 n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.]]> Wed 22 Mar 2023 15:25:15 AEDT ]]> Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34208 −8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.]]> Wed 04 Sep 2019 09:48:47 AEST ]]> New genetic loci link adipose and insulin biology to body fat distribution https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28089 Sat 24 Mar 2018 07:39:47 AEDT ]]> Genetic studies of body mass index yield new insights for obesity biology https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27460 −8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.]]> Sat 24 Mar 2018 07:32:44 AEDT ]]> Partitioning heritability by functional annotation using genome-wide association summary statistics https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23306 Sat 24 Mar 2018 07:16:19 AEDT ]]>