20 October 2017

When Do Higher Tax Rates Lead To Lower Tax Collections?

The Laffer curve peak at which higher tax rates lead to lower tax revenues is quantified for 27 OECD countries here. It ranges from top marginal rates of 60% to 76% by country, with the U.S. at the highest end of that range, and Luxembourg at the low end. Top rates exceed the Laffer curve peak as estimated by this study in Austria, Belgium, Denmark, Finland and Sweden. Sweden is the furthest beyond this peak.

Czechia (46%), Mexico (33%), New Zealand (44%) and Poland (47%) are the only countries with a lower top marginal rate than the U.S. (48%) by this methodology. The top rate in the U.S. is lower relative to its Laffer curve peak than every other OECD country except Slovakia which ties it at 30% and Mexico which is at 28%.

The notion that the U.S. has uncompetitively high tax rates relative to its economic peers is simply not born out by the evidence.

19 October 2017

ASGH 2017 Abstracts

The abstracts of the conference presentations at the American Society of Human Genetics Conference in Orlando, Florida for 2017 which is currently in progress is available here. It sorts by first digit of the paper number so, for example, 2, 20, 201 and 2001 are all adjacent to each other. Plenary and platform talks have numbers up to 372. Higher numbers are poster-presentations.

General observation. Lots of studies looked at whether disease predictive tools like risk scores work across ancestry lines. Generally they do, but often they omit additional ancestry specific genes with similar phenotypic consequences.

14 Sperm have more de novo mutations than other kinds of cells
Various sporadic human diseases, ranging from autism spectrum disorders to congenital heart disease and muscular dystrophies, are caused by de novo mutations. In a classical model, these are assumed to occur at a low rate in the parental germ cells (10-4-10-8). Consequently, de novo mutations identified by genetic testing are often assigned a low risk of recurrence in siblings. This idea is increasingly challenged by the detection of mosaicism in the parents. However, previous studies were largely restricted to the analysis of somatic tissues, whose genetic information is, by definition, not transmitted to the next generation. Here, we directly assessed the presence of inherited “de novo” mutations in paternal sperm and discovered abundant, germline restricted mosaicism. These samples were collected from a panel of fourteen families with a proband presenting with autism spectrum disorder. For all of these a candidate de novomutation had been identified in our ongoing genetic studies of this disorder. Employing digital droplet PCR, the causative variants were detectable in 4 sperm samples, but virtually absent or drastically reduced in the somatic tissue for 3. The latter mutations were present a high allelic fractions (AF), comprising SNVs in NR2F1 (AF=8%) and GRIN2A (AF=15%), as well as a large deletion of CACNG2 (AF=10%). As a consequence, the GRIN2A variant, despite being undetectable in the father by classical genetic testing, was inherited by three siblings presenting with phenotypes consistent with this mutation.
We next used deep whole genome sequencing (90x) of matched sperm and blood samples of four fathers to test for germline mosaicism of all de novo variants present in the offspring. 5-10% of these mutations were detectable in the paternal sperm, half of which were absent or at very low levels (<2%) in the matched blood. These data, together with an unbiased analysis employing mosaic variant detection algorithms, suggest that germline-specific or germline-enriched mosaicism is currently underestimated. This information has important potential implications for clinical practice. Based on our results, genetic analysis of sperm has the potential to quantify individualized recurrence risks for affected families, but could also have predictive value for prospective fathers.
18 Alternative splicing of brain-expressed transcripts distinguishes major adult psychiatric disorders

19 Sexually dimorphic DNA methylation in human brain and relevance to psychiatric disorders

134 Gene x environment links between obesity and depression

204 Migraine risk inheritance patterns in Finland

216 Genome testing is very useful in treating NICU patients

1033 Genetics of child onset psychosis

1038 Gene associated with intellectual disability with severe self-harm

1048 DNA testing determines cause of 30% of intellectual disability cases not otherwise determinable

1287 Estimating contamination in DNA samples without doing comparisons

1314 Estimating genetic condition frequency with a combination of determination of frequency in people with monogenetic cause disease and review of population sample of genomes

1461 Infant development is affected by their microbiomes.

1596 Large, long term study evaluates stroke risk

1611 Search for opiod addiction gene in white women

1612 New markers for schizophrenia severity (about 80% hereditary)

1700 Genes involved in disorders of sex development (e.g. hemaphrodites)

2059 FASD (Fetal Alcoholism Spectrum Disorder) is indistinguishable from ADHD and has genetic origins rather that prenatal alcohol exposure origins; FAS (Fetal Alcohol Syndrome) has an environmental cause and is very distinct from FASD and ADHD.

2099 Some ADHD genes found in African-Americans are not found in other populations. A stable 6%-7% of kids are diagnosed with ADHD which is 75% to 90% genetic. (One of the other studies notes an 80% persistence from childhood to adulthood.)

2144 Genetics of ADHD hyperactivity/impulsivity and inattention dimensions are quite different

2199 Most lifespan benefits of education are mediated through smoking or not

2468 DNA studies of kids with ADHD are worth it 8%-13% of the time.

2523 Discusses mosaicism and chimerism in humans

2579 Aging as measured by telomeres in preschoolers already differs based on sex and race in New Zealand children

2767 BMI is 48%-60% hereditary

2842 Alcoholism is 50%-65% hereditary