Alzheimer's gene linked to increased fecundity in women

Having one or two APOE-ε4 alleles, a genetic variant associated with increased risk of Alzheimer's and cardiovascular disease, has been linked to a larger number of offspring in women in Bolivia.

Previous studies have linked genetic variants that can be deleterious to humans living in urban environments, such as BRCA1/2 which can increase risk of breast cancer, to increased fecundity in women. Similarly, children with APOE-ε4 alleles have been shown to grow faster than those who do not, in Brazil. Researchers from Arizona decided to look at the potential impact of the APOE-ε4 allele on number of offspring among women in an indigenous population in Bolivia called the Tsimané, who have natural fertility patterns, with women having nine children on average. The study was published in August in Science Advances.

'Despite the fact the allele has these negative impacts, it still occurs in between 15 to 25 percent of the population across Europe and the US,' said Dr Benjamin Trumble, from the Centre for Evolution and Medicine of Arizona State University and first author of the recent study.

'What we found in this population was that women began reproducing almost a year earlier if they had the APOE-ε4 allele, and they had shorter interbirth intervals. Those two things combined allow them to have about half an additional kid.'

The team collected data on age at onset of menstruation, age at first birth, total number of births, and interval between births of 795 girls and women in the community, aged between 13 and 90 years old. Their distribution of the APOE alleles roughly reflected that of the general population. Twenty percent had at least one APOE-ε4 allele.

Women with at least one copy of APOE-ε4 first gave birth on average 10 months earlier than those with no APOE-ε4. Their time between births was nearly two months shorter. As a result, they found that women with at least one copy of the APOE-ε4 allele had between 0.3-0.5 more children over their lifetime than those without. Women with two copies of APOE-ε4 had 1.4-2 more children.

Women with at least one copy of APOE-ε4 were also around half as likely to self-report experiencing a miscarriage, and were on average 1.8kg heavier. While increased uptake of cholesterol is associated with disease in older age, it can be an important advantage in the survival of young mothers and babies in nature.

'We need to better understand global variation, and in particular, we need to kind of think outside the box and move beyond our focus on "this allele causes X disease" and that's just how it is. Instead, we need to take a step back and say, "What about in different environments?" Because that actually opens up a whole other possibility for prevention or treatment,' Dr Trumble said.