Comment by thirdacc | Hacker News Reader

Comment by thirdacc | Hacker News Reader

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I don't think ADHD in particular is caused by unrelated stuff. The heritability findings are pretty strong.

> A study of 894 ADHD probands and 1135 of their siblings aged 5–17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3, 4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control children [4].

> Twin studies rely on the difference between the within-pair similarities of monozygotic (MZ) twin pairs, who are genetically identical, and dizygotic (DZ) twin pairs, who share, on average, 50% of their segregating genes. The mean heritability across 37 twin studies of ADHD or measures of inattentiveness and hyperactivity is 74% (Fig. 1). A similar heritability estimate of around 80% was seen in a study of MZ and DZ twins, full siblings, and maternal and paternal half-siblings [5]. The heritability is similar in males and females and for the inattentive and hyperactive-impulsive components of ADHD [6,7,8].

https://www.nature.com/articles/s41380-018-0070-0

"ADHD has been clearly linked with numerous environmental risk factors, particularly around the prenatal and perinatal period. Some of the most robust risk factors identified are maternal prenatal health conditions and psychological distress (e.g. hypertension, obesity, pre-eclampsia, immune activation), in utero exposure to poor diet (with critical factors still being determined), teratogenic effects of certain medications (e.g. acetaminophen) and environmental exposures (e.g. lead), as well as neonatal factors such as prematurity and low birth weight [27]. Other extreme exposures in the postnatal environment (such as extreme infant emotional neglect) have also been associated with an ADHD syndrome [28, 29]."

Cecil, C. A. M., & Nigg, J. T. (2022). Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential. Molecular diagnosis & therapy, 26(6), 581–606. https://doi.org/10.1007/s40291-022-00609-y

"The convincing evidence for genes as risk factors for ADHD does not exclude the environment as a source of etiology. The fact that twin estimates of heritability are less than 100% asserts quite strongly that environmental factors must be involved. ADHD’s heritability is high, and that estimate encompasses gene by environment interaction. Thus, it is possible that such interactions will account for much of ADHD’s etiology. Environmental risk factors likely work through epigenetic mechanisms, which have barely been studied in ADHD [148]. The importance of the environment can also be seen in the fact that, as for other complex genetic disorders, much of ADHD’s heritability is explained by SNPs in regulatory regions rather than coding regions [149]."

Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular psychiatry, 24(4), 562–575. https://doi.org/10.1038/s41380-018-0070-0

Isnt this explained simply by families who are aware of, willing, capable of disgnosing their children are more likely to tske another child to a diagnosis vs a random child?

Granted they did have a control for adopted siblings

Twin studies are explicitly about scrolling for this kind of family bias.

"twin studies fail to separate the effects of genes and the prenatal environment. This failure casts doubt on claims of the relative effects of genes and environment on intelligence, psychiatric disorders, personality and other psychological variables, and other conditions."

https://www.psychologytoday.com/gb/blog/looking-in-the-cultu...

"Although many twin studies have been conducted (which is quite an understatement; there are almost 9,000 hits for “twin study” on PubMed!), there have long been critics who argue that they are scientiﬁcally worthless."

Smith, Jinkinson. (2020). The debate over twin studies: an overview. http://dx.doi.org/10.22541/au.159674847.78026661

"Because heritability is defined by both genetic and environmental influences, it is not a fixed characteristic of a disease or trait, but a population-specific estimate, analogous to, for example, the mean height, cholesterol level or life expectancy in a population. It also cannot be interpretated at the family or individual level."

Kaprio J. (2012). Twins and the mystery of missing heritability: the contribution of gene-environment interactions. Journal of internal medicine, 272(5), 440–448. https://doi.org/10.1111/j.1365-2796.2012.02587.x

(How) did they control for parental influence vs. genetic heritability? I grew up with a pathologically anxious mother. I still remember having to counteract her behaviour to avoid it leaking into my world, before I managed to move out. She is still a trigger for me, 30 years later. I can only stand having her around me for at max. 2 hours, then my vessel is full. IMO, I am not convinced that a sibling study rules out environmental influences.

They had a control for adoptive siblings. The critic in me says, ok what was their age of adoption, do parents perhaps treat adopted children differently, do adopted children perhaps grow behaviors unindicative of ADHD, does the knowledge that its genetic influence the diagnoses themself?

The age of adoption seems crucial to rule out early childhood trauma induced by the parents. I actually know mine, although it took me 35 years to get my mother to admit what happened. My point, I am very skeptical when it comes to parents reflecting on the bad influences they might have had on the development of their child. After all, bad parenting has a pretty harsh stigma in society (and it should!)

Yes but if the SAME behaviour emerges regardless of parenting style then that is significant

The twin studies would largely control for that.

Ahem, sorry for being slow and/or stupid, but how? Aren't both twins exposed to the same parental style?

Not if they’re raised in different families.

In studies of monozygotic twins (shared genetic predisposition), typically the twins were raised in different environments (adoption, etc.). If behavior among the twins is divergent then environmental factors are likely predominant. OTOH if concordance of traits is strongly evident, behavior is attributable to genetic factors.

My understanding is that separating children from their biological parents has wide-reaching consequences, even if done in a non-traumatic way, and even if they are ultimately raised by a different set of parents. I would imagine the trauma originating from having to be adopted could be a uniquely triggering factor for genetic predisposition in the case of only one of the twins. How would twin studies be able to account for that?

I agree. Also, the prenatal environment (9 months of development!) and circumstances of birth, which both twins share, is not accounted for at all. Or rather, it is accounted for as "heritability" by twin studies, which is plainly wrong.

https://williamjbarry.substack.com/p/the-first-1000-days

No need for family separation. You simply compare the correlation between monozygotic ("identical") twins vs dizygotic ("non-identical") twins.

For example, monozygotic twins will always have the same eye color (99+% correlation), while dizygotic twins do not. Thus we can conclude eye color is genetic. Both twins are raised by their respective parents, so it's unlikely parenting is causing this difference in eye-color-correlation.

"twin studies fail to separate the effects of genes and the prenatal environment. This failure casts doubt on claims of the relative effects of genes and environment on intelligence, psychiatric disorders, personality and other psychological variables, and other conditions."

https://www.psychologytoday.com/gb/blog/looking-in-the-cultu...

"Although many twin studies have been conducted (which is quite an understatement; there are almost 9,000 hits for “twin study” on PubMed!), there have long been critics who argue that they are scientiﬁcally worthless."

Smith, Jinkinson. (2020). The debate over twin studies: an overview. http://dx.doi.org/10.22541/au.159674847.78026661

"Because heritability is defined by both genetic and environmental influences, it is not a fixed characteristic of a disease or trait, but a population-specific estimate, analogous to, for example, the mean height, cholesterol level or life expectancy in a population. It also cannot be interpretated at the family or individual level."

Kaprio J. (2012). Twins and the mystery of missing heritability: the contribution of gene-environment interactions. Journal of internal medicine, 272(5), 440–448. https://doi.org/10.1111/j.1365-2796.2012.02587.x

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