A Reevaluation of the 1990 “Minnesota Study of Twins Reared Apart” IQ Study

In 1990, Thomas J. Bouchard, Jr. and colleagues published the widely cited 1990 “Minnesota Study of Twins Reared Apart” (MISTRA) Science IQ study. To arrive at the conclusion that “IQ is strongly affected by genetic factors,” Bouchard and colleagues omitted their control group reared-apart dizygotic twin (“DZA”) IQ-score correlations. Near-full-sample correlations published after the study’s 2000 endpoint show that the reared-apart monozygotic twin (“MZA”) and DZA group IQ correlations did not differ at a statistically significant level, suggesting that the study failed the first step in determining that IQ scores are influenced by heredity. After bypassing the model-fitting technique they used in most non-IQ MISTRA studies, the researchers assumed that the MZA group IQ-score correlation alone “directly estimates heritability.” This method was based on unsupported assumptions by the researchers, and they largely overlooked the confounding influence of cohort effects. Bouchard and colleagues then decided to count most environmental influences they did recognize as genetic influences. I conclude that the MISTRA IQ study failed to discover genetic influences on IQ scores and cognitive ability across the studied population, and that the study should be evaluated in the context of psychology’s replication problem.

An Epidemiologic, Longitudinal, and Discordant-Twin Study of the Association Between Gambling Disorder and Suicidal Behaviors

Gambling disorder is associated with suicidal behaviors, but it is not clear whether the association is due to common etiologic factors or to gambling disorder being causally related to suicidality. This question was examined from the perspective of epidemiologic, longitudinal, and discordant-twin studies. The results suggested that the causes of the association with disordered gambling differed for suicidal ideation, plan, and attempt and differed for men and women. The association of suicidal thoughts with disordered gambling was noncausally explained by common genetic influences among women but not men. Conversely, there was evidence consistent with a potentially causal influence of disordered gambling on suicide attempt among men but not women, which might have been related to gambling-related financial problems. The use of monetary data to identify individuals experiencing financial harms associated with their gambling may represent a more practicable target for screening, intervention, and prevention and may reduce gambling-related financial crises, thereby warding off a potential gambling-related suicide attempt.

Shared genetic influences on depression and menopause symptoms

Background Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a genome-wide association study (GWAS) of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank. Methods The analysis included 232 993 women aged 39–71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD. Results GWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause [top rs77322567, odds ratio (OR) = 0.78, p = 7.7 × 10−15]. Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression (rg = 0.231, s.e.= 0.055, p = 2.8 × 10−5). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications. Conclusions These results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3) are effective treatments for hot flashes.

The Heritability of Cognitive Aging: A Systematic Review of Longitudinal Twin Studies

Heritability of cognitive ability changes across late adulthood, although whether genetic variance increases or decreases in importance is not understood well. We performed a systematic review of the heritability of cognitive ability derived from longitudinal twin studies of middle-aged and older adult twins. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles were identified in APA PsycINFO and Clarivate Web of Science electronic databases. Identified articles were screened by title and abstract; remaining full-text articles were then fully evaluated. Reference sections served as an additional method for identification of relevant articles. In total, 3,106 articles were identified and screened, 28 of which were included and were based on data from 10 longitudinal twin studies published from 1994-2021. There are large genetic influences on an initial level of cognitive performance across domains whereas there are small to moderate genetic influences on change in performance with age. Evidence was less definitive about whether the same or different genetic factors contribute to both level and change. Non-shared environmental influences appeared to drive individual changes in cognitive performance. Heritability tended to either be stable or decline after 65 years, possibly because of the increasing importance of non-shared environmental influences on cognitive ability. Recent studies report increases in heritability across specific subtests and domains. Shared environmental variance accounted for little variance in cognitive ability. Emerging research questions and future directions for understanding genetic and environment influences in the context of gene-environment interplay are highlighted in this review.

Case Studies of Two Classical Imprinting Growth Disorders: Silver–Russell and Beckwith–Wiedemann Syndromes

The genetic influences on human growth are being increasingly deciphered. Silver–Russell and Beckwith–Wiedemann syndromes (SRS; BWS) are two relatively common genetic syndromes with under- and overgrowth-related issues being the reason for referral. Aberration in genomic imprinting is the underlying genetic pathomechanism behind these syndromes. Herein, we described a series of children with these two growth disorders and give an orientation to the reader of the concept of imprinting as well as the genetic testing strategy and counseling to be offered in these syndromes.

Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life

Background: Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. Better understanding changes across life in the determinants of BMI may inform etiology, the timing of preventative efforts, and the interpretation of increasing number of studies utilizing genetically-informed designs to study BMI. We thus used a birth cohort study to investigate differences in association and explained variance in the polygenic prediction of BMI from infancy to old age (2-69 years) in a single sample. A secondary aim was to investigate how a key purported environmental influence on BMI (childhood socioeconomic position) differed across life, and whether it operated independently and/or multiplicatively of genetic influences. Methods: Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured weight and height from infancy to old age (12 timepoints from 2-69 years) and genetic data (obtained from blood samples at 53 years). We derived three polygenic indices derived from GWAS of a) adult BMI, b) recalled childhood body size, and c) childhood-adolescence BMI. We investigated associations of each polygenic index and BMI at each age and compared in terms of absolute effect size and explained variance (R2). We used linear and quantile regression models, and finally investigated the additive or multiplicative role of childhood socioeconomic position. Results: Mean BMI and its variance increased across adulthood. For polygenic liability to higher adult BMI (Khera et al), the trajectories of effect size (beta) and explained variance (R-squared) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Conclusion: Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance (non-shared) environmental influences on BMI across life.