Inbreeding depression and IQ in a study of 72 countries

Woodley, Michael A.

doi:10.1016/j.intell.2008.10.007

Cited by 31 publications

(25 citation statements)

References 38 publications

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“…Beyond methodological considerations, we confirmed in this study known associations between increased inbreeding and reduced lung function (PEF), cognitive ability (FIS and MTCIM), and fertility (NCF), which were previously reported, however, using different proxy traits (10,(29)(30)(31). We also replicated the association between inbreeding and decreased height (b UNI − LDMS: −1.71 phenotypic SD for complete inbreeding; P = 0.003) even though it was below the Bonferroni threshold.…”

Section: Discussionsupporting

confidence: 88%

Detection and quantification of inbreeding depression for complex traits from SNP data

Yengo

Zhu

Wray

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

106

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Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in ∼140,000 participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between −2.3 and −5.2 phenotypic SDs for complete inbreeding; P < 0.001). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.M ating between close relatives has detrimental consequences on the survival and fertility of resulting offspring (1). This overall reduction of fitness, referred to as inbreeding depression (ID), is observable in a wide range of organisms, including plants (2), animals (3, 4), and humans (5). In humans, major abnormalities are more frequent in children from consanguineous marriages (6) and genes causing rare diseases can be mapped by ascertaining children from such matings (7). To date, although the genetic basis of ID is not completely elucidated, two main hypotheses are proposed to explain this phenomenon: homozygosity for partially recessive deleterious mutations and heterozygous advantage (overdominance) (1, 8). More generally, ID can be estimated for any complex trait, even if the trait is not an obvious component of fitness. For polygenic traits, ID can be detected if there is directional dominance (DD) across loci, which means that the phenotype of individuals who are heterozygous deviates from the average phenotypes of homozygous individuals in a consistent direction. For fitness components, DD is negative; i.e., on average homozygosity reduces fitness.In practice, ID can be estimated from pedigree studies when the relationships between parents are known (6, 9). However, given the limited number and the small sizes of such studies in humans, contemporary efforts (5, 10) to quantify ID have instead used SNP genotyping platforms to directly estimate inbreeding coefficients (F). SNP data may allow a more accurate evaluation of inbreeding (11), in particular for distant and cryptic inbreeding, and allow inference to be drawn from large population data (10). Conceptually, once a measure of F is derived from SNP data, ID can subsequently be estimated by correlating phenotype with the estimated F.Genome-wide estimators of F fall in two categories: average homozygosity measures across loci (irrespective of position) and measures of continuous runs of homozygosity (ROH). Using ROH, ID has been reported for diseas...

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Section: Discussionsupporting

confidence: 88%

Detection and quantification of inbreeding depression for complex traits from SNP data

Yengo

Zhu

Wray

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

106

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“…They found cross-national correlations of r ¼ 20.77 (n ¼ 35, p , 0.0001) and r ¼ 20.62 (n ¼ 71, p , 0.01), respectively, between average IQ and measures of inbreeding. Woodley (2009), however, noted that rates of consanguineous marriage itself may not account for the magnitude of this variation because (i) the statistical significance of the effect disappears when education and gross domestic product (GDP) are controlled for, and (ii) the effect of inbreeding on intelligence had previously been shown to be relatively small.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Parasite prevalence and the worldwide distribution of cognitive ability

2010

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In this study, we hypothesize that the worldwide distribution of cognitive ability is determined in part by variation in the intensity of infectious diseases. From an energetics standpoint, a developing human will have difficulty building a brain and fighting off infectious diseases at the same time, as both are very metabolically costly tasks. Using three measures of average national intelligence quotient (IQ), we found that the zero-order correlation between average IQ and parasite stress ranges from r ¼ 20.76 to r ¼ 20.82 (p , 0.0001). These correlations are robust worldwide, as well as within five of six world regions. Infectious disease remains the most powerful predictor of average national IQ when temperature, distance from Africa, gross domestic product per capita and several measures of education are controlled for. These findings suggest that the Flynn effect may be caused in part by the decrease in the intensity of infectious diseases as nations develop.

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“…This nominal association with increased cognitive ability is counterintuitive when compared with the results from more extreme inbreeding based on pedigree information. [1][2][3] A potential explanation for this direction of effect is that individuals with higher cognitive ability might show greater positive assortative mating, which would lead to increased homozygosity at loci for higher cognitive ability in their offspring. However, in a separate sample we showed that greater positive assortative mating was not associated with higher cognitive ability.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] The presumed mechanism is that detrimental recessive mutations are more likely to be identical by descent in the offspring of such unions and so have a greater chance of being expressed. To date, research on the relationship between inbreeding and cognitive ability has largely been restricted to recent inbreeding events as determined by pedigree, although one genome-wide study of ancestral inbreeding has been reported for 10 unrelated families each with two mentally retarded siblings.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

et al. 2013

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The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin-cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P ¼ 0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P ¼ 0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.

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Inbreeding depression and IQ in a study of 72 countries

Cited by 31 publications

References 38 publications

Detection and quantification of inbreeding depression for complex traits from SNP data

Detection and quantification of inbreeding depression for complex traits from SNP data

RETRACTED: Parasite prevalence and the worldwide distribution of cognitive ability

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

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