Despite the high heritability of many brain measures (h2 up to 0.89; Kremen et al. 2009; or even up to 0.96: van Soelen et al. 2012), the specific genetic variants that contribute to this variability remain largely unknown. A possible exception is the Alzheimer’s disease (AD) risk gene, APOE: carriers of one or more risk-conferring alleles (APOE4) demonstrate accelerated gray matter loss with age (Lu et al. 2011). They also have a roughly three-fold increased risk for late-onset AD, for each risk allele they carry (Corder et al. 1993). In a recent meta-analysis of 35 prospective cohort studies with an average follow-up of 2.9 years, the odds ratio for conversion from mild cognitive impairment to Alzheimer’s dementia in APOE4 carriers was determined to be 2.29, relative to non-carriers (Elias-Sonnenschein et al. 2011). Other prior papers reported a higher odds ratio, around 4 for heterozygotes and >7 for homozygotes, with some differences depending on the ancestry of the cohort. According to another more recent review, one copy of ApoE4 increases risk by ~2.6–3.4, and homozygotes for ApoE4 have an odds ratio of 14.9 compared to the reference genotype of E3/3 (Liu et al. 2013).
