Chunk #50 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.1 Are endophenotype effect sizes larger than those of other phenotypes?
from the body surface, fare no better. The ENIGMA consortium (Thompson et al., 2014) combined GWAS data across multiple samples and conducted a meta-analysis of hippocampal and intracranial volume from structural MRI in a discovery sample of 7,795 individuals and multiple replication samples altogether totaling 21,151 (Stein et al., 2012). They found two genome-wide significant loci. The top hit explained 0.27% of the variance in hippocampal volume, slightly less than the 0.34% of the variance in BMI accounted for by the top hit in FTO described above. Perhaps it is unsurprising that genetic effects on the size of brain regions are similar in magnitude to genetic effects on the size of the entire body. Finally, perhaps the most widely studied electrophysiological endophenotype of relevance to psychopathology is resting heart rate. This endophenotype has been studied in 38,991 individuals, finding nine associated variants in six loci, accounting for between .083-.167% of variance in resting heart rate (Eijgelsheim et al., 2010), again less than the top hit in FTO for BMI.
