Dataset Information

Bias in Mendelian randomization due to assortative mating.

ABSTRACT: Mendelian randomization (MR) has been increasingly used to strengthen causal inference in observational epidemiology. Methodological developments in the field allow detecting and/or adjusting for different potential sources of bias, mainly bias due to horizontal pleiotropy (or "off-target" genetic effects). Another potential source of bias is nonrandom matching between spouses (i.e., assortative mating). In this study, we performed simulations to investigate the bias caused in MR by assortative mating. We found that bias can arise due to either cross-trait assortative mating (i.e., assortment on two phenotypes, such as highly educated women selecting taller men) or single-trait assortative mating (i.e., assortment on a single phenotype), even if the exposure and outcome phenotypes are not the phenotypes under assortment. The simulations also indicate that bias due to assortative mating accumulates over generations and that MR methods robust to horizontal pleiotropy are also affected by this bias. Finally, we show that genetic data from mother-father-offspring trios can be used to detect and correct for this bias.

SUBMITTER: Hartwig FP

PROVIDER: S-EPMC6221130 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bias in Mendelian randomization due to assortative mating.

Hartwig Fernando Pires FP Davies Neil Martin NM Davey Smith George G

Genetic epidemiology 20180703 7

Mendelian randomization (MR) has been increasingly used to strengthen causal inference in observational epidemiology. Methodological developments in the field allow detecting and/or adjusting for different potential sources of bias, mainly bias due to horizontal pleiotropy (or "off-target" genetic effects). Another potential source of bias is nonrandom matching between spouses (i.e., assortative mating). In this study, we performed simulations to investigate the bias caused in MR by assortative ...[more]

PMID: 29971821

Similar Datasets

Project description:BackgroundSex pheromone communication systems may be a major force driving moth speciation by causing behavioral reproductive isolation via assortative meeting of conspecific individuals. The 'E' and 'Z' pheromone races of the European corn borer (ECB) are a textbook example in this respect. 'Z' females produce and 'Z' males preferentially respond to a 'Z' pheromone blend, while the 'E' race communicates via an 'E' blend. Both races do not freely hybridize in nature and their populations are genetically differentiated. A straightforward explanation would be that their reproductive isolation is a mere consequence of "assortative meeting" resulting from their different pheromones specifically attracting males towards same-race females at long range. However, previous laboratory experiments and those performed here show that even when moths are paired in a small box - i.e., when the meeting between sexual partners is forced - inter-race couples still have a lower mating success than intra-race ones. Hence, either the difference in attractivity of E vs. Z pheromones for males of either race still holds at short distance or the reproductive isolation between E and Z moths may not only be favoured by assortative meeting, but must also result from an additional mechanism ensuring significant assortative mating at close range. Here, we test whether this close-range mechanism is linked to the E/Z female sex pheromone communication system.Methodology/principal findingsUsing crosses and backcrosses of E and Z strains, we found no difference in mating success between full-sisters emitting different sex pheromones. Conversely, the mating success of females with identical pheromone types but different coefficients of relatedness to the two parental strains was significantly different, and was higher when their genetic background was closer to that of their male partner's pheromone race.Conclusions/significanceWe conclude that the close-range mechanism ensuring assortative mating between the E and Z ECB pheromone races is unrelated to the difference in female sex pheromone. Although the nature of this mechanism remains elusive, our results show that it is expressed in females, acts at close range, segregates independently of the autosome carrying Pher and of both sex chromosomes, and is widely distributed since it occurs both in France and in the USA.

Dataset Information

Bias in Mendelian randomization due to assortative mating.

Publications

Bias in Mendelian randomization due to assortative mating.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets