A population genetic analysis of male homosexuality

As a companion to the previous post, I pass along this article by Ciani et al. arguing that only a two-locus genetic model for male homosexuality with at least one locus on the X chromosome, in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness), accounts for all the known empirical data. That data is interesting (as described in this account in Slate):

It starts with four curious patterns. First, male homosexuality occurs at a low but stable frequency in a wide range of societies. Second, the female relatives of gay men produce children at a higher rate than other women do. Third, among these female relatives, those related to the gay man's mother produce children at a higher rate than do those related to his father. Fourth, among the man's male relatives, homosexuality is more common in those related to his mother than in those related to his father.

Increasing complexity of nerve synapses during evolution

Nicholas Wade points to the work of Grant and colleagues on how the complexity of nerve interconnections (synapses) has increased during evolution as the variety of their protein components has increased from a few to several hundred. Vertebrate synapses have about 1,000 different proteins, assembled into 13 molecular machines, one of which is built from 183 different proteins. The human brain has about 100 billion neurons, interconnected at 100 trillion synapses. Grant provides an analogy:

If the synapses are thought of as the chips in a computer, then brainpower is shaped by the sophistication of each chip, as well as by their numbers...From the evolutionary perspective, the big brains of vertebrates not only have more synapses and neurons, but each of these synapses is more powerful — vertebrates have big Internets with big computers and invertebrates have small Internets with small computers.

The top part of the figure (click to enlarge) shows the phylogenetic relationships of the species studied. The number of varieties of two signaling complexes, NMDA receptor (NRC or MASC) / postsynaptic density (PSD) are in parentheses. The lower half shows the occurrences of PSD and MASC homologs found in each of the 19 species as a percentage of those found in human.

Another reason for being gay?

Ever alert for the latest speculation on a possible biological basis for why I might be gay, I come across this little gem on fruitflies: genetic manipulation that enhances dopamine levels in males makes them more likely to court with other males.

Brain changes in dyslexia - different in Hong Kong and Chicago

Siok et al show that the brain changes associated with dyslexia in an alphabetic versus an ideographic language can be different. In alphabetic language, a reader sees a letter and associates it with a sound. Chinese characters correspond to syllables and require much more memorization. Both Chinese and English dyslexics find it harder to make their way through even fairly simple written material. This study suggests that their brain mechanics as they try to read may be as different as Chinese is from English. Here is their abstract:

Developmental dyslexia is a neurobiologically based disorder that affects approximately 5–17% of school children and is characterized by a severe impairment in reading skill acquisition. For readers of alphabetic (e.g., English) languages, recent neuroimaging studies have demonstrated that dyslexia is associated with weak reading-related activity in left temporoparietal and occipitotemporal regions, and this activity difference may reflect reductions in gray matter volume in these areas. Here, we find different structural and functional abnormalities in dyslexic readers of Chinese, a nonalphabetic language. Compared with normally developing controls, children with impaired reading in logographic Chinese exhibited reduced gray matter volume in a left middle frontal gyrus region previously shown to be important for Chinese reading and writing. Using functional MRI to study language-related activation of cortical regions in dyslexics, we found reduced activation in this same left middle frontal gyrus region in Chinese dyslexics versus controls, and there was a significant correlation between gray matter volume and activation in the language task in this same area. By contrast, Chinese dyslexics did not show functional or structural (i.e., volumetric gray matter) differences from normal subjects in the more posterior brain systems that have been shown to be abnormal in alphabetic-language dyslexics. The results suggest that the structural and functional basis for dyslexia varies between alphabetic and nonalphabetic languages.

Negligent mouse moms - a model for humans?

From the laboratory of my Univ. of Wisconsin Zoology colleague Steve Gammie, along with Anthony Auger in the Psychology Department, an interesting account of a mouse model for human maternal neglect: a strain of mice that exhibit unusually high rates of maternal neglect, with approximately one out of every five females failing to care for her offspring. By comparing the good mothers to their less attentive relatives, this group has found that negligent parenting seems to have both genetic and non-genetic influences, and may be linked to dysregulation of the brain signaling chemical dopamine. In more detail, they:

...examined brain activity in neglectful and nurturing mice. c-Fos expression was significantly elevated in neglectful relative to nurturing mothers in the CNS, particularly within dopamine associated areas, such as the zona incerta (ZI), ventral tegmental area (VTA), and nucleus accumbens. Phosphorylated tyrosine hydroxylase (a marker for dopamine production) was significantly elevated in ZI and higher in VTA (although not significantly) in neglectful mice. Tyrosine hydroxylase levels were unaltered, suggesting a dysregulation of dopamine activity rather than cell number. Phosphorylation of DARPP-32, a marker for dopamine D1-like receptor activation, was elevated within nucleus accumbens and caudate-putamen in neglectful versus nurturing dams.

Heritability of cooperative behavior

A study of the behaviors of monozygotic versis dizygotic twins (i.e. 'identical' vs. 'non-identical' twins) in a classical cooperation game yields evidence for genetic influences on yet another of our behaviors - how trusting we are:

Although laboratory experiments document cooperative behavior in humans, little is known about the extent to which individual differences in cooperativeness result from genetic and environmental variation. In this article, we report the results of two independently conceived and executed studies of monozygotic and dizygotic twins, one in Sweden and one in the United States. The results from these studies suggest that humans are endowed with genetic variation that influences the decision to invest, and to reciprocate investment, in the classic trust game. Based on these findings, we urge social scientists to take seriously the idea that differences in peer and parental socialization are not the only forces that influence variation in cooperative behavior.

Our results are complementary to work on the neurological and hormonal substrates of behavior in the trust game and other similar social dilemma games...Enhanced oxytocin levels have been documented in subjects who received a monetary transfer that reflected an intention of trust, and later work has demonstrated that exogenously administered oxytocin increases trust. Scholars have also documented associations between cortisol and trust. These hormonal studies, therefore, indicate that further study of polymorphisms of CYP11B1, OXTR, and other genes involved in the expression and regulation of these hormones may explain part of the genetic effect on cooperation. In fact, one research team has already identified a polymorphism in the AVPR1a gene that is associated with related behavior in the dictator game.

The Genetics of Personality and Well-Being

Some support for our folk wisdom that happiness is a personal(ity) thing: Weiss et al. have used standard verbal and written questionnaires to examine personality and subjective well-being in 973 twin pairs. The written personality questionnaire used the five factor model (FFM) rating neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness. Numerous studies of personality have shown that genetic effects account for approximately 50% of the variance in these FFM domains. The 'happiness' measure was by a telephone interview that asked three questions: how satisfied participants were with life at the present, how much control subjects felt they had over their lives, and how satisfied they were with life overall.

They found that the genetic structure of the FFM and subjective well-being could be modeled without genetic influences specific to subjective well-being. Subjective well-being was genetically indistinct from personality traits, especially those reflecting, in part, emotional stability (low neuroticism), social and physical activity (high extraversion), and constraint (high conscientiousness). The close genetic relationship between positive personality traits and happiness traits is the mirror image of comorbidity in psychopathology. Weiss et al. suggest that their findings indicate that subjective well-being is linked to personality by common genes and that personality may form an "affective reserve" relevant to set-point maintenance and changes in set point over time.

Poetry in your genome?

Now that we are able to synthesize complete genomes for organisms, we can also write what we want in its individual genes. Andrew Pollack describes several such literary efforts:

You were expecting poetry, perhaps? The secret messages hidden in J. Craig Venter’s synthetic bacterial genome have now been revealed. They are Dr. Venter’s name, and that of his research institute and co-workers....Dr. Venter announced last week in the journal Science that his team had become the first to synthesize the complete DNA of a bacterium. He revealed that the genome had five “watermarks,” sequences of genetic code that would spell words using the letters for the amino acids that would be produced by the DNA...Wired Science reported Monday that it had ferreted out the messages, with help from government scientists. One watermark said “VenterInstitvte,” using the unusual spelling because there is no amino acid represented by the letter “u.”...The other messages were CraigVenter, HamSmith, GlassandClyde and CindiandClyde for his co-authors Hamilton O. Smith, Clyde A. Hutchison III, John I. Glass and Cynthia Andrews-Pfannkoch. A Venter spokeswoman confirmed them...In 2003, scientists from Icon Genetics, a German biotechnology company, engineered the plant Arabidopsis thaliana to contain a line from Virgil’s “Georgics,” with the meaning “Neither can every soil bear every fruit.”

Newborn humans: predisposition for biological motion

This work demonstrates that when we are born, we have an innate bias towards attending to motions characteristic of other living things. Newborn chickens do this also. The abstract, a figure, and a video from Simion et al. :

An inborn predisposition to attend to biological motion has long been theorized, but had so far been demonstrated only in one animal species (the domestic chicken). In particular, no preference for biological motion was reported for human infants of less than 3 months of age. We tested 2-day-old babies' discrimination after familiarization and their spontaneous preferences for biological vs. nonbiological point-light animations. Newborns were shown to be able to discriminate between two different patterns of motion (Exp. 1) and, when first exposed to them, selectively preferred to look at the biological motion display (Exp. 2). This preference was also orientation-dependent: newborns looked longer at upright displays than upside-down displays (Exp. 3). These data support the hypothesis that detection of biological motion is an intrinsic capacity of the visual system, which is presumably part of an evolutionarily ancient and nonspecies-specific system predisposing animals to preferentially attend to other animals.

Figure: Three sample frames taken from the animation sequences used in the study: the biological motion stimulus (i.e., the walking hen) (Top), the nonbiological motion stimulus (random motion) (Middle), and the inverted biological motion display (upside-down walking hen) (Bottom). Squares indicate the point-lights.

GENES R US

This clip from the Jan. 20 issue of Science:

Personal genomics revved into high gear last year thanks to DNA chips that make it possible to cheaply scan the entire genome (Science, 21 December 2007, p. 1842). You can track the flood of new discoveries at SNPedia (www.snpedia.com), a Web site run by two biotech veterans in Bethesda, Maryland, that catalogs SNPs culled from the literature.

SNPs are single-nucleotide polymorphisms: single-base variations in DNA that researchers are tying to traits and disease risks. Browse by medical conditions (77 so far) and discover, for example, that carrying two copies of the T version of a SNP called rs2273535 raises your risk of colon cancer by 50%; another SNP, rs6152, is associated with baldness. Visitors can also search by genetically influenced drug reactions (48) and genes (128). There are links to relevant papers and sites (including James Watson's and J. Craig Venter's respective genomes) and to blogs by people who are sending their DNA to a lab to be "SNP chipped." The site is also a wiki, which means anyone can contribute.

The site "could be a very valuable research tool," says computational biologist Mark Daly of the Broad Institute in Cambridge, Massachusetts. "It will be great to see how this develops."

We Differ More Than We Thought

This essay by Mark Pagel is worth passing on in its entirety:

The last thirty to forty years of social science has brought an overbearing censorship to the way we are allowed to think and talk about the diversity of people on Earth. People of Siberian descent, New Guinean Highlanders, those from the Indian sub-continent, Caucasians, Australian aborigines, Polynesians, Africans — we are, officially, all the same: there are no races.

Flawed as the old ideas about race are, modern genomic studies reveal a surprising, compelling and different picture of human genetic diversity. We are on average about 99.5% similar to each other genetically. This is a new figure, down from the previous estimate of 99.9%. To put what may seem like miniscule differences in perspective, we are somewhere around 98.5% similar, maybe more, to chimpanzees, our nearest evolutionary relatives.

The new figure for us, then, is significant. It derives from among other things, many small genetic differences that have emerged from studies that compare human populations. Some confer the ability among adults to digest milk, others to withstand equatorial sun, others yet confer differences in body shape or size, resistance to particular diseases, tolerance to hot or cold, how many offspring a female might eventually produce, and even the production of endorphins — those internal opiate-like compounds.

We also differ by surprising amounts in the numbers of copies of some genes we have. Modern humans spread out of Africa only within the last 60-70,000 years, little more than the blink of an eye when stacked against the 6 million or so years that separate us from our Great Ape ancestors. The genetic differences amongst us reveal a species with a propensity to form small and relatively isolated groups on which natural selection has often acted strongly to promote genetic adaptations to particular environments.

We differ genetically more than we thought, but we should have expected this: how else but through isolation can we explain a single species that speaks at least 7,000 mutually unintelligible languages around the World?

What this all means is that, like it or not, there may be many genetic differences among human populations — including differences that may even correspond to old categories of 'race' — that are real differences in the sense of making one group better than another at responding to some particular environmental problem. This in no way says one group is in general 'superior' to another, or that one group should be preferred over another. But it warns us that we must be prepared to discuss genetic differences among human populations.

Nature versus Nurture in Ventral Visual Cortex

Polk et al. do functional magnetic resonance imaging of monozygotic and dizygotic twins to show that genetics play a significant role in determining the cortical response to faces and places, more so than to orthographic stimuli (chairs or pseudowords). Here is their abstract, a paragraph from their concluding section and one figure from the paper.

Using functional magnetic resonance imaging, we estimated neural activity in twins to study genetic influences on the cortical response to categories of visual stimuli (faces, places, and pseudowords) that are known to elicit distinct patterns of activity in ventral visual cortex. The neural activity patterns in monozygotic twins were significantly more similar than in dizygotic twins for the face and place stimuli, but there was no effect of zygosity for pseudowords (or chairs, a control category). These results demonstrate that genetics play a significant role in determining the cortical response to faces and places, but play a significantly smaller role (if any) in the response to orthographic stimuli.


Figure legend: Patterns of estimated neural activity when viewing the four stimulus categories (axial slice). Functional activation maps were computed for the four contrasts of interest (faces, houses, pseudowords, and chairs relative to the phase-scrambled control condition), and the similarity measures (r) between these functional maps were computed for each twin pair. (Click on figure to enlarge)

The results of this study demonstrate that genetics play a significant role in determining the cortical response to faces and places. Of course, these findings do not imply that experience plays no role in determining the observed activity. To take just one example, genes that affect social behavior could potentially lead some people to look at faces and places more than other people, and the resulting difference in experience could lead to changes in the neural circuitry (we thank one of the anonymous reviewers for this example). The results simply demonstrate that genetics do play a crucial role. The results also show that genetics play a significantly smaller role in determining the cortical response to visually presented orthographic stimuli. Overall, the findings are consistent with the view that the cortical substrates of face recognition and place recognition are partially innately specified, but that the cortical response to orthographic stimuli is more dependent on experience. Face and place recognition are older than reading on an evolutionary scale, they are shared with other species, and they provide a clearer adaptive advantage. It is therefore plausible that evolution would shape the cortical response to faces and places, but not orthographic stimuli.

Human genetic variation - breakthrough of the year

We differ from each other in the number and order of our genes, and in their composition. A few edited clips from E. Pennisi's summary of Science Magazine's breakthrough of the year in the Dec. 21 issue:

There are an estimated 15 million places along our genomes where one base can differ from one person or population to the next. By mid-2007, more than 3 million such locations, known as single-nucleotide polymorphisms (SNPs), had been charted. Called the HapMap, this catalog has made the use of SNPs to track down genes involved in complex diseases--so-called genome-wide association studies--a reality....New gene associations now exist for type I and II diabetes, heart disease, breast cancer, restless leg syndrome, atrial fibrillation, glaucoma, amyotrophic lateral sclerosis, multiple sclerosis, rheumatoid arthritis, colorectal cancer, ankylosing spondylitis, and autoimmune diseases. One study even identified two genes in which particular variants can slow the onset of AIDS, demonstrating the potential of this approach for understanding why people vary in their susceptibility to infectious diseases.

Genomes can differ in many other ways. Bits of DNA ranging from a few to many thousands, even millions, of bases can get lost, added, or turned around in an individual's genome. Such revisions can change the number of copies of a gene or piece of regulatory DNA or jam two genes together, changing the genes'products or shutting them down. This year marked a tipping point, as researchers became aware that these changes, which can alter a genome in just a few generations, affect more bases than SNPs....In one study, geneticists discovered 3600 so-called copy number variants among 95 individuals studied. Quite a few overlapped genes, including some implicated in our individuality--blood type, smell, hearing, taste, and metabolism, for example. Individual genomes differed in size by as many as 9 million bases.

Learning from errors - genetic differences between humans

From Holden's brief summary of the work:

"Once burned, twice shy" works for most people. But some people are slow to learn from bad experiences.

This work shows that:

...people with a particular gene variant have more difficulty learning via negative reinforcement.
...demonstrates that a single-base-pair difference in the genome is associated with a remarkably different ability to learn from past mistakes is quite an accomplishment
...combines brain imaging with a task in which participants chose between symbols on a computer screen,
...centers on the A1 variant, or allele, of the gene encoding the D2 receptor, a protein on the surface of brain cells activated by the neurotransmitter dopamine. Earlier studies have hinted that this variant alters the brain's reward pathways and thereby makes people more vulnerable to addictions.

Brain activity was monitored (color) as a subject chose between two symbols (inset) and was rewarded with a smiley or frowny face. In the left panel the lower colors are hippocampus, the upper one the posterior medial frontal cortex.

Here is the abstract from Klein et al.

The role of dopamine in monitoring negative action outcomes and feedback-based learning was tested in a neuroimaging study in humans grouped according to the dopamine D2 receptor gene polymorphism DRD2-TAQ-IA. In a probabilistic learning task, A1-allele carriers with reduced dopamine D2 receptor densities learned to avoid actions with negative consequences less efficiently. Their posterior medial frontal cortex (pMFC), involved in feedback monitoring, responded less to negative feedback than others' did. Dynamically changing interactions between pMFC and hippocampus found to underlie feedback-based learning were reduced in A1-allele carriers. This demonstrates that learning from errors requires dopaminergic signaling. Dopamine D2 receptor reduction seems to decrease sensitivity to negative action consequences, which may explain an increased risk of developing addictive behaviors in A1-allele carriers.

Genetic variation in the enhancement of intelligence by breastfeeding.

It's the environment AND the genes...Caspi et al. provide a fascinating example of how genetic differences can moderate the effects of environmental influences on an individuals' health and behavior. The authors chose breastfeeding as the environmental exposure because the biological processes underlying its benefits for the developing brain are increasingly well understood. Here are some edited clips from the paper:

The predominant long-chain polyunsaturated fatty acids (LC-PUFAs) present in human milk, but not in cow's milk or most infant formulas, are docosahexaenoic acid (DHA; 22:6n-3) and arachidonic acid (AA or ARA; 20:4n-6). Substantial amounts of DHA and AA accumulate in the human brain during the first postnatal months, and infants who are breastfed have higher concentrations of DHA and AA than infants fed unsupplemented formulas. Evidence, in general, is consistent with the hypothesis that LC-PUFAs in breast milk may enhance cognitive development. In humans, children who are breastfed have higher IQs than children not fed breast milk, and this advantage persists into adulthood.

The authors chose to study people with two allelic variants of FADS2, which they termed C and G. FADS2 is an attractive candidate gene because of its role in the modification of dietary fatty acids. FADS2, located on chromosome 11q12.2, encodes the delta-6 desaturase that is the rate-limiting step on the metabolic pathway leading to AA and DHA production.

Examination of different cohorts of several thousand children from ongoing longitudinal studies in New Zealand, England and Wales revealed that breastfed children carrying the C allele showed a 6.4-IQ-point advantage relative to children not fed breast milk. GG homozygotes neither gained an advantage from breastfeeding nor suffered a disadvantage from not being fed breast milk. The authors ruled out alternative explanations of the finding involving gene–exposure correlation, intrauterine growth, social class, and maternal cognitive ability, as well as maternal genotype effects on breastfeeding and breast milk.

...the finding has implications for the public understanding of genetics. The pendulum of opinion surrounding nature versus nurture has swung back and forth, yielding global estimates of heritability versus "environmentality" that have overlooked the contribution of interactions between specific genes and specific experiences. To date, research on gene–environment interactions has been dominated by the search for genetic variants that increase disease susceptibility to environmental pathogens; for example, carriers of "short" 5-HTT alleles who encounter stressful life events are at risk of becoming depressed; carriers of "rapid" NAT2 alleles who eat red meat are at risk of developing colorectal cancer. However, genes are not only implicated in disease; here we have shown that a genetic variant (in FADS2) may also enhance a favorable response (increased IQ) to a salubrious exposure present throughout human ancestry (breastfeeding).

Do you really want to know your own genome?

Nicholas Wade offer a brief essay in the Nov. 16 New York Times which notes several companies, such as DeCode Genetics, 23andMe, and Navigenics that are now offering to give you an analysis of your own individual genome for $1000 or less. While knowing that you have a gene that predisposes you to a given disease might reinforce life style choices that make that disease less likely (in the case of potential heart disease, for example, converting from red meat and potatoes to complex carbohydrates) such information could also cause needless alarm, for many factors other than genotype contribute to actual outcomes in each of us.

Genetics and tonal languages

It is likely that there are heritable differences of brain structure and function that affect language acquisition and usage...cognitive biases in a population of acquirers could influence the direction of language change across generations. These biasing effects could result in linguistic differences between populations, producing nonspurious (causal) correlations between genetic and linguistic diversities. Dediu and Ladd:

... propose that the linguistic typology of tone is affected by such a bias. Human languages differ typologically in the way they use voice fundamental frequency (pitch). All languages use consonants and vowels to distinguish one word or grammatical category from another, but, in addition, so-called "tone languages" (e.g., Chinese) use pitch for this purpose as well, whereas "non-tone languages" (e.g., English) use pitch only at sentence level (to convey emphasis, emotion, etc.). In tone languages, that is, pitch is organized into tone phonemes that are functionally comparable with consonant and vowel phonemes. Tone languages are the norm in sub-Saharan Africa and are very common in continental and insular southeast Asia. They are rare in the rest of Eurasia, North Africa, and Australia. They are relatively common in Central America, the Caribbean, and the Amazon basin, and occur sporadically elsewhere among the aboriginal languages of the Americas..

Here is their Abstract:

The correlations between interpopulation genetic and linguistic diversities are mostly noncausal (spurious), being due to historical processes and geographical factors that shape them in similar ways. Studies of such correlations usually consider allele frequencies and linguistic groupings (dialects, languages, linguistic families or phyla), sometimes controlling for geographic, topographic, or ecological factors. Here, we consider the relation between allele frequencies and linguistic typological features. Specifically, we focus on the derived haplogroups (note: these are sets of nucleotide polymorphisms) of the brain growth and development-related genes ASPM and Microcephalin, which show signs of natural selection and a marked geographic structure, and on linguistic tone, the use of voice pitch to convey lexical or grammatical distinctions. We hypothesize that there is a relationship between the population frequency of these two alleles and the presence of linguistic tone and test this hypothesis relative to a large database (983 alleles and 26 linguistic features in 49 populations), showing that it is not due to the usual explanatory factors represented by geography and history. The relationship between genetic and linguistic diversity in this case may be causal: certain alleles can bias language acquisition or processing and thereby influence the trajectory of language change through iterated cultural transmission.

Williams Syndrome - evidence for a discrete social brain

David Dobbs offers a very well written essay (PDF here) on Williams Syndrome in the Sunday New York Times Magazine (7/8/07). The syndrome is caused by a well-defined deletion in chromosome 7 that occasionally occurs during the synthesis of egg or sperm cells. Patients have a low IQ (~60) and compromised spatial skill and analytical thought, but are hyper-sociable and friendly, very talkative. An pathway from the orbitofrontal (OFC) cortex to the amygdala that usually signals dangerous or angry faces is inactive; but curiously the OFC-amygdala connection still works normally for nonsocial threats such as pictures of snakes, sharks or car crashes. The existence of this syndrome provides perhaps the strongest evidence for genetically and developmentally distinct class of 'social brain' mechanisms distinct from other higher sensory, motor, and analytical skills.

Gene crucial to learning and memory unique in humans

Zu et al report that a human-specific gene mutation (not seen in other primates) leads to the origin of a novel splice form of neuropsin (KLK8), a protein involved in learning and memory. This may be one of the genes that have been positively selected during human evolution Their abstract:

Neuropsin (kallikrein 8, KLK8) is a secreted-type serine protease preferentially expressed in the central nervous system and involved in learning and memory. Its splicing pattern is different in human and mouse, with the longer form (type II) only expressed in human. Sequence analysis suggested a recent origin of type II during primate evolution. Here we demonstrate that the type II form is absent in nonhuman primates, and is thus a human-specific splice form. With the use of an in vitro splicing assay, we show that a human-specific T to A mutation (c.71-127T>A) triggers the change of splicing pattern, leading to the origin of a novel splice form in the human brain. Using mutation assay, we prove that this mutation is not only necessary but also sufficient for type II expression. Our results demonstrate a molecular mechanism for the creation of novel proteins through alternative splicing in the central nervous system during human evolution.

Genetic basis for vulnerability to drug addiction.

Yacubian et al.(link to full text) demonstrate that human genetic variations that alter dopamine neurotransmission involved in reward pathways correlate with change in sensitivity to rewards and also with activity in the ventral striatum reward system. The data suggest a potential genetic basis for drug vulnerability. Here is their abstract:

Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual differences in ventral striatal sensitivity for value were in part explained by an epistatic gene–gene interaction between COMT and DAT. Although most genotype combinations exhibited the expected activity increase with more likely and larger rewards, two genotype combinations (COMT Met/Met DAT 10R and COMT Val/Val 9R) were associated with blunted ventral striatal responses. In view of a consistent relationship between reduced reward sensitivity and addiction, our findings point to a potential genetic basis for vulnerability to addiction.