Friday, October 31, 2008

Evolutionary perspective on the genetics of osteoporosis

This review paper in Human Genetics discusses osteoporosis from an evolutionary and genetic perspective, and sometimes reads like a list of personal health guidelines (which is ok, I guess). I'm usually pretty reserved when it comes to criticizing papers on my blog, but I'm going to make an exception and say that this paper was somewhat disappointing, especially given that it was published in a high level journal: Human Genetics.
Ok, so first the obligatory point about how we are "stone age bodies living in a novel, modern world":
" ... current demographic trends will have the effect of altering what was once a positive adaptation for distinctive human bipedality into a serious set of “collateral” pathology among the modern elderly (Latimer 2005)."
...then a brief mention on the source of population differences: (I don't like the "Africans" generalization)
"Therefore, Africans more frequently have lactose intolerance, probably because they do not need as much vitamin D and calcium to maintain their (relatively strong) skeletons. On the contrary, skin depigmentation and high consumption of dairy products do not seem to protect Northern Europeans from fractures."
They also go on to explain the mechanism by which consumption of whole grain and milk products likely aggravates the risk of osteoporosis, which is pretty interesting.

He then briefly moves on to the genetics of osteoporosis with this statement which I find a bit hard to swallow, maybe just because I'm a too much of a hard-core adaptationist:
"It seems accurate to assume that if osteoporosis has a genetic determinant, its genetics will share peculiarity with the aging per se, being an example of “post-reproductive” genetics (Capri et al. 2008), which is difficult to explain by a selection process."
He argues that there would have been no selection against osteoporotic phenotypes since these cause problems later in life and would have no effect early in life, an argument which leaves me unconvinced:
"Therefore, children with a “pro-osteoporotic” bone architecture and lower bone mineralization were not selected against—which means, they were able to transfer their genes further on."
At the end of the paper are statements about the future of evolution in humans (which generally make me cringe):
"Is natural selection still a driving force in humans, given that our survival is often less dependent on genes than on technology?"
Osteoporosis: an evolutionary perspective
David Karasik
Human Genetics early online
Abstract: Increased life expectancy has led to an overall aging of the population and greater numbers of elderly people. Therefore, the number of people with osteoporosis has increased substantially, accompanied with an epidemic of hip fractures. Osteoporosis is an age-related systemic condition that naturally occurs, among mammals, only in humans. Osteoporosis is known to be highly heritable. However, assuming a genetic determinant for this post-reproductive disease to be transmitted from one generation to the next is counter-intuitive, based on the principles of human evolution, I will attempt to provide an explanation of the phenomenon from the point of view of evolution, selection, and changed environment in humans, which contributed to human longevity, while on other hand, contribute to diseases of civilization, including osteoporosis. There is a need to delve into evolution of human species in search for adaptive patterns to a specific environment that humans are operating in the last couple of millennia, to clarify whether “good” and “bad” genes exist, and how to find and correct them. The answer to the above questions will help us to identify causes of the current epidemic of osteoporosis and to pin-point a tailored treatment.

Tuesday, October 28, 2008

Predicting unobserved phenotypes from genotypic data

This looks really interesting. The goal is to use whole genome SNP data to predict three phenotypes in mice (coal color, % of CD8+ cells, cellular hemoglobin), using "reversible jump MCMC". According to this website this is how RJMCMC works:
"– RJMCMC randomly “walks around” the space of possible model structures by changing one edge at a time – called structurallearning.
– At each step in its “walk”, all of the model parameters are updated
– called parametrical learning.
– At the end, you have a list of all of the model structures it visited at each step and their corresponding set of parameters."
They cite this recent paper that I posted about a few months ago that proposes a different way of looking simultaneously at the association between a collection of SNPs and some trait.
So, in this paper, they seem to be able to make decent predictions about these traits using about 12,000 SNPs in each of 2,300 mice. The correlations between observed and expexted phenotypes, using only genotype data, are in the range of .33 to .85.
There's really a lot of interesting things in this paper and I don't have to go over all of them.
I'll just end by mentioning that, as the authors state, if we were to do this in humans we would probably need many more markers and more individuals since the mice used in this experiment were from inbred lines with extended LD.

Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
Sang Hong Lee, Julius H. J. van der Werf, Ben J. Hayes, Michael E. Goddard, Peter M. Visscher
PLoS Genet 4(10): e1000231.
Abstract: Genome-wide association studies (GWAS) for quantitative traits and disease in humans and other species have shown that there are many loci that contribute to the observed resemblance between relatives. GWAS to date have mostly focussed on discovery of genes or regulatory regions habouring causative polymorphisms, using single SNP analyses and setting stringent type-I error rates. Genome-wide marker data can also be used to predict genetic values and therefore predict phenotypes. Here, we propose a Bayesian method that utilises all marker data simultaneously to predict phenotypes. We apply the method to three traits: coat colour, %CD8 cells, and mean cell haemoglobin, measured in a heterogeneous stock mouse population. We find that a model that contains both additive and dominance effects, estimated from genome-wide marker data, is successful in predicting unobserved phenotypes and is significantly better than a prediction based upon the phenotypes of close relatives. Correlations between predicted and actual phenotypes were in the range of 0.4 to 0.9 when half of the number of families was used to estimate effects and the other half for prediction. Posterior probabilities of SNPs being associated with coat colour were high for regions that are known to contain loci for this trait. The prediction of phenotypes using large samples, high-density SNP data, and appropriate statistical methodology is feasible and can be applied in human medicine, forensics, or artificial selection programs.

Friday, October 24, 2008

Another study on European genetic structure

...this time focused on Northern Europe, and especially Finland, using 250,000 SNPs, STRUCTURE, MDS plots and other measures of population differentiation.
see Dienekes' post for STRUCTURE output, and other comments.

Wednesday, October 22, 2008

I wanted to do this!! - Eating behavior at Chinese buffets

Dang!!, I've always wanted to do a study like this, but these researchers beat me to the punch. The things they look at here are pretty interesting (and frankly, pretty funny), but they could have looked at the types of foods people were eating (ex: meat vs. other), SES, ethnicity etc.... Of course that would entail more complicated data collection... This reminds me of this great study.

Eating behavior and obesity at Chinese buffets.
Wansink B, Payne CR.
Obesity 2008 Aug;16(8):1957-60.
Abstract: The aim of this study was to investigate whether the eating behaviors of people at all-you-can-eat Chinese buffets differs depending upon their body mass. The resulting findings could confirm or disconfirm previous laboratory research that has been criticized for being artificial. METHODS AND PROCEDURES: Trained observers recorded the height, weight, sex, age, and behavior of 213 patrons at Chinese all-you-can-eat restaurants. Various seating, serving, and eating behaviors were then compared across BMI levels. RESULTS: Patrons with higher levels of BMI were more likely to be associated with using larger plates vs. smaller plates (OR 1.16, P less than 0.01) and facing the buffet vs. side or back (OR 1.10, P less than 0.001). Patrons with higher levels of BMI were less likely to be associated with using chopsticks vs. forks (OR 0.90,P less than 0.05), browsing the buffet before eating vs. serving themselves immediately (OR 0.92, P less than 0.001), and having a napkin on their lap vs. not having a napkin on their lap (OR 0.92, P less than 0.01). Patrons with lower BMIs left more food on their plates (10.6% vs. 6.0%, P less than 0.05) and chewed more per bite of food (14.8 vs. 11.9, P less than 0.001). DISCUSSION: These observational findings of real-world behavior provide support for laboratory studies that have otherwise been dismissed as artificial.

Tuesday, October 21, 2008

Hispanics and Alzheimer's: article in New York Times

It looks like Hispanics have a disproportionately high prevalence of Alzheimer's and tend to develop it earlier, according to research cited in this New York Times article.
Genetic reasons are not favored, at least according to what the author of the article, Pam Belluck has gleaned:
"It is not that Hispanics are more genetically predisposed to Alzheimer’s, say experts, who say the diversity of ethnicities that make up Hispanics or Latinos make a genetic explanation unlikely."
...and what this researcher has found:
Dr. Rafael A. Lantigua, a professor of clinical medicine at Columbia University Medical School, said, “There’s no gene at this point that we can say this is just for Latinos.” Dr. Lantigua added that one gene that increased Alzheimer’s risk was less prevalent in Latinos than non-Hispanic whites.
More favored explanations are SES, "cultural dislocation", and depression.
The author goes on to describe several studies that have examined the etiology of population differences in Alzheimer's, one of them finding that higher acculturation to American society among Mexican Americans was associated with higher Alzheimer's risk.

Sunday, October 19, 2008

Selection may not be responsible for worldwide variation in circadian clock genes

some suggestive evidence, at most (look here for related post about PER2 gene variation):

Genetic differences in human circadian clock genes among worldwide populations.
Ciarleglio CM, Ryckman KK, Servick SV, Hida A, Robbins S, Wells N, Hicks J, Larson SA, Wiedermann JP, Carver K, Hamilton N, Kidd KK, Kidd JR, Smith JR, Friedlaender J, McMahon DG, Williams SM, Summar ML, Johnson CH.
J Biol Rhythms. 2008 Aug;23(4):330-40.
Abstract: The daily biological clock regulates the timing of sleep and physiological processes that are of fundamental importance to human health, performance, and well-being. Environmental parameters of relevance to biological clocks include (1) daily fluctuations in light intensity and temperature, and (2) seasonal changes in photoperiod (day length) and temperature; these parameters vary dramatically as a function of latitude and locale. In wide-ranging species other than humans, natural selection has genetically optimized adaptiveness along latitudinal clines. Is there evidence for selection of clock gene alleles along latitudinal/photoperiod clines in humans? A number of polymorphisms in the human clock genes Per2, Per3, Clock, and AANAT have been reported as alleles that could be subject to selection. In addition, this investigation discovered several novel polymorphisms in the human Arntl and Arntl2 genes that may have functional impact upon the expression of these clock transcriptional factors. The frequency distribution of these clock gene polymorphisms is reported for diverse populations of African Americans, European Americans, Ghanaians, Han Chinese, and Papua New Guineans (including 5 subpopulations within Papua New Guinea). There are significant differences in the frequency distribution of clock gene alleles among these populations. Population genetic analyses indicate that these differences are likely to arise from genetic drift rather than from natural selection.

Thursday, October 16, 2008

Lipid profiles and African ancestry

Previous research has found that African ancestry is associated with healthier lipid profiles, compared to European ancestry, and that people of African descent in the UK have lower coronary heart disease compared to whites. Since sex also mediates the risk of cardiovascular disease, this study investigates four variants on the Y-chromosome, in "579 men of different ethnic groups (blacks, South Asians, and whites) from UK and in 301 whites in Italy." All Black and South Asian men were first generation immigrants, so that might be why they don't do any kind of adjustment for differing admixture proportions. Given their conclusion:
"In our study, the men of black African origin carrying the A alleles of both TBL1Y and USP9Y had a more favorable lipoprotein profile, characterized by lower levels of serum triglycerides and higher levels of HDL-cholesterol, thus indicating the existence of a “cardio-protective haplotype.” In contrast, in white men, both from the UK and Italy, and in people of South Asian origin, the lipoprotein profiles were not affected by these genotypes."
...they then have a pretty good discussion of the weaknesses and alternative explanations of their findings. They don't really discuss any kind of adaptive or evolutionary explanation for the population differences, other than to mention, regarding which alleles are ancestral, that:
"The data presented here suggest that G allele of TBL1Y and T allele of USP9Y, reported as the wild-type alleles in whites ( may be derived from the A alleles of both genes, which are the most frequent in black people of African origin."
Genetic Variants of Y Chromosome Are Associated With a Protective Lipid Profile in Black Men
Paola Russo; Alfonso Siani; Michelle A. Miller; Sharada Karanam; Teresa Esposito; Fernando Gianfrancesco; Gianvincenzo Barba; Fabio Lauria; Pasquale Strazzullo;Francesco P. Cappuccio
Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1569.

Abstract Objective— Gender and ethnicity modulate the phenotypic expression of cardiovascular risk factors. In particular, men are at higher risk of developing cardiovascular diseases compared to women, whereas black populations of African origin display reduced mortality from coronary heart disease (CHD) as compared to both whites and South Asians. Because the male-specific region (MSY) of the human Y chromosome is an obvious candidate for gender-related differences in the development of cardiovascular diseases, we aimed to identify genetic variants of MSY influencing cardiovascular risk profile in different ethnic groups. Methods and Results— We genotyped 4 polymorphisms of MSY (HindIII±, rs768983 of TBL1Y, rs3212292 of USP9Y, and rs9341273 of UTY genes) in 579 men of different ethnic groups (blacks, South Asians, and whites) from UK and in 301 whites in Italy. We found that the TBL1YA USP9YA haplotype, present only in blacks in whom it represents the most frequent allelic combinations (AA: n=125; all other combinations: n=45), was associated with lower levels of triglycerides (P=0.025) and higher levels of HDL-cholesterol (P=0.005) as compared to the other haplotypes. Conclusion— The TBL1YA USP9YA haplotype of the Y chromosome, present only in black people of African origin, attributes a favorable lipoprotein pattern, likely to contribute to their reduced susceptibility to coronary heart disease. The study evaluated the association of genetic variants of the male-specific region of the Y chromosome with cardiovascular risk factors in different ethnic groups. The most frequently observed haplotype in black people was associated with a favorable lipoprotein pattern, thus contributing to the lower rate of cardiovascular diseases in blacks.

Wednesday, October 15, 2008

Baldness genetics

Dan at Genetic Future has a great post on a couple of recent genome-wide association studies on male pattern baldness.

Tuesday, October 14, 2008

Genetic determinants of Vitamin D levels among Hispanics and African Americans

This study has a large diverse sample and they look at the association between variants in three vitamin D related genes and vitamin D levels in the blood. They find an association between variants in the DBP (vitamin D Binding Protein gene) and plasma levels of 25(OH)D and 1,25(OH)2D in all three populations. I wonder how these polymorphisms differ in frequency and haplotype structure between groups.

Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans.
Corinne D. Engelman, Tasha E. Fingerlin, Carl D. Langefeld, Pamela J. Hicks, Stephen S. Rich, Lynne E. Wagenknecht, Donald W. Bowden and Jill M. Norris
The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 9 3381-3388
Context: Vitamin D deficiency is associated with many adverse health outcomes, yet little is known about the genetic epidemiology of vitamin D or its metabolites. Objective: Our objective was to examine the relationship among three vitamin D-related genes and levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in Hispanics (HAs) and African Americans (AAs). Design and Setting: The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited and examined subjects in: Los Angeles, California (AAs; 513 individuals from 42 families); San Luis Valley (SLV), Colorado (HAs; 513 individuals from 30 families); and San Antonio (SA), Texas (HAs; 504 individuals from 58 families). Main Outcome Measures: Plasma levels of 25(OH)D and 1,25(OH)2D were measured. Results: Levels of 25(OH)D were highest in SLV-HAs [18.3 ± 7.7 ng/ml (45.7 ± 19.2 nmol/liter)], lower in SA-HAs [14.6 ± 6.4 ng/ml (36.4 ± 16.0 nmol/liter)], and lowest in AAs [11.0 ± 5.4 ng/ml (27.5 ± 13.5 nmol/liter)]. Levels of 1,25(OH)2D were similar in AAs [43.5 ± 13.9 pg/ml (113.1 ± 36.1 pmol/liter)] and SLV-HAs [43.2 ± 13.3 pg/ml (112.3 ± 34.6 pmol/liter)], but higher in SA-HAs [48.6 ± 17.0 pg/ml (126.4 ± 44.2 pmol/liter)]. After adjusting for gender and age within the site, two single nucleotide polymorphisms (SNPs) in the vitamin D binding protein gene (DBP), rs4588 and rs7041, were associated with 25(OH)D, and one SNP in the DBP, rs4588, was associated with 1,25(OH)2D at all three study centers. Conclusions: SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)2D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.

Thursday, October 09, 2008

Why was lactase persistence selected for?

This paper has been discussed by Razib at GNXP, and probably others. I thought I would take a closer look at it myself.
One of the main findings here is the north-south gradient within England in the frequency of the lactase persistence allele.
But they also examine relationships between this genotype and health measures in order to uncover the mechanism by which lactase persistence may have been selected for.
For example, did lactase persistence arise due to the benefits (sugar, protein, fat) or because it enabled one to avoid the ill effects of lactose non-persitence (adverse health reactions)? In this paper, they test for associations between the LCT genotype and various health-related measures.
They also have a good discussion about the selection pressures that may have led to the lactase persistence trait being favored. Among the hypotheses, many of which I had never heard of, as outlined in the paper:

1) "nutritional (and survival) advantage of milk consumption in populations that have milk availability"

2) "the calcium absorption hypothesis which considers the ability to use milk as of particular importance for high latitude
populations with low ultraviolet light exposure who are thus subject to potential vitamin D deficiency and poor calcium absorption and for whom the calcium absorption-stimulating effect of lactose would increase fitness."

3) "a reduced diarrhoeal disease mortality hypothesis that considers that, in populations that have become high consumers of milk, this consumption will increase risk of diarrhoeal disease in individuals who are not lactase persistent and thus select for lactase persistence"

4) specifically for African populations: "in arid regions with animal husbandry practices allowing access to milk, the ability to use milk has a selective advantage through the provision of water and electrolytes"

5) "the enhanced fertility by early weaning hypothesis that postulates that lactase persistence leads to earlier weaning and that earlier cessation of breastfeeding reduces the infertile period following each birth"

It doesn't seem like this study provides any conclusive or even suggestive evidence in favor or against any of these hypotheses, although there is some data that does goes against the diarrhea hypothesis:
"the consequences of prolonged childhood diarrhoeal disease that might be expected in survivors – shorter body height, leg length and perhaps higher blood pressure – were not seen in our data"
Lactase persistence-related genetic variant: population substructure and health outcomes
George Davey Smith, Debbie A Lawlor, Nic J Timpson, Jamil Baban, Matt Kiessling, Ian N M Day and Shah Ebrahim
European Journal of Human Genetics advance online
Abstract: Lactase persistence is an autosomal-dominant trait that is common in European-derived populations. A basic tendency for lactase persistence to increase from the southeast to the northwest across European populations has been noted, but such trends within countries have not been extensively studied. We genotyped the C/T-13910 variant (rs4988235) that constitutes the putatively causal allele for lactase persistence (T allele representing persistence) in a general population sample of 3344 women aged 60–79 years from 23 towns across Britain. We found an overall frequency of 0.253 for the C (lactase non-persistence) allele, but with considerable gradients of decreasing frequency from the south to the north and from the east to the west of Britain for this allele. Daily sunlight was positively related to C (non-persistence) allele prevalence. However, sunlight exposure and latitude are strongly correlated, and it was not possible to identify which is the primary factor statistically underlying the distribution of lactase persistence. The C/T-13910 variant (rs4988235) was not related to drinking milk or bone health (although drinking milk itself was protective of bone health), and was essentially unrelated to a wide range of other lifestyle, health and demographic characteristics. One exception was general health being rated as being poor or fair, for which there was an odds ratio of 1.38 (1.04, 1.84) for women homozygous for the C allele; on adjustment for latitude and longitude of place of birth, this attenuated to 1.19 (0.87, 1.64). The lactase persistence variant could contribute to the examination of data for the existence of, and then statistical control for, population substructure in genetic association studies.

Wednesday, October 08, 2008

Adipose tissue expandability explains onset of metabolic syndrome?

When studying disease traits it is always preferable to understand all elements of the etiological pathway.
A recent paper in PLoS Biology titled "It's Not How Fat You Are, It's What You Do with It That Counts" describes the "Adipose Expandability Hypothesis" as a way of explaining why some individuals develop metabolic syndrome and why others don't, regardless of how obese they are. What matters is your ability to store fat. If you're good at it you can stave off further health complications. If you're not good at it, you start storing fat in organ tissue, leading to further health complications even if you have no excess body fat.

Sunday, October 05, 2008

Predicting hair color from genes

It seems like we're getting closer to understanding the genetic basis of traits like skin, hair and eye pigmentation. Although it is generally assumed that it will be difficult to fully grasp the genetics of complex traits, it could be within reach in the near-term for these types of traits. Understanding the genetic basis of these traits will provide some guiding principles for uncovering the genetic basis of more 'complex' complex traits, as well as about the evolutionary genetic process, population histories, and interactions with environmental factors.
So what do we learn from this paper (see abstract below) on the association between SLC45A2 variants and hair color among Polish subjects?
First, from the intro, with respect to predicting red hair color:
"Nowadays, red hair phenotype is being predicted using
assays that rely on examination of the single MC1R gene, and this allows correct inference in more than 90% of cases (Grimes et al. 2001; Branicki et al. 2007)."
Back to this study, they basically find a rare variant in SLC45A2 that increases a person's odds of having black hair by about seven.

"However, in the present study, 3.6% of red-haired individuals were found to have the L374 allele associated with darker pigmentation. All of them had two MC1R alterations, which are considered as major function mutations strongly affecting receptor performance (data not present). All these individuals had fair skin and blue eyes. This indicates a predominant role of the MC1R gene."
Association of the SLC45A2 gene with physiological human hair colour variation
Wojciech Branicki, Urszula Brudnik, Jolanta Draus-Barini, Tomasz Kupiec and Anna Wojas-Pelc
Journal of Human Genetics Early online
Abstract: Pigmentation is a complex physical trait with multiple genes involved. Several genes have already been associated with natural differences in human pigmentation. The SLC45A2 gene encoding a transporter protein involved in melanin synthesis is considered to be one of the most important genes affecting human pigmentation. Here we present results of an association study conducted on a population of European origin, where the relationship between two non-synonymous polymorphisms in the SLC45A2 gene — rs26722 (E272K) and rs16891982 (L374F) — and different pigmentation traits was examined. The study revealed a significant association between both variable sites and normal variation in hair colour. Only L374F remained significantly associated with hair colour when both SNPs were included in a logistic regression model. No association with other pigmentation traits was detected in this population sample. Our results indicate that the rare allele L374 significantly increases the possibility of having black hair colour (OR = 7.05) and thus may be considered as a future marker for black hair colour prediction.

Wednesday, October 01, 2008

Ancient origin of genes associated with human genetic disease

via Dienekes, an interesting paper on the temporal origin of disease-related genes.

An ancient evolutionary origin of genes associated with human genetic diseases
Tomislav Domazet-Loo and Diethard Tautz
Molecular Biology and Evolution
Abstract: Several thousand genes in the human genome have been linked to a heritable genetic disease. The majority of these appear to be non-essential genes (i.e. are not embryonically lethal when inactivated) and one could therefore speculate that they are late additions in the evolutionary lineage towards humans. Contrary to this expectation, we find that they are in fact significantly over-represented among the genes that have emerged during the early evolution of the metazoa. Using a phylostratigraphic approach, we have studied the evolutionary emergence of such genes at 19 phylogenetic levels. The majority of disease genes was already present in the eukaryotic ancestor and the second largest number has arisen around the time of evolution of multicellularity. Conversely, genes specific to the mammalian lineage are highly underrepresented. Hence, genes involved in genetic diseases are not simply a random subset of all genes in the genome, but are biased towards ancient genes.

Ethnicity, genetic variant at KCNMB1, sex, and asthma

An african-specific functional polymorphism in KCNMB1 shows sex-specific association with asthma severity.
Seibold MA, Wang B, Eng C, Kumar G, Beckman KB, Sen S, Choudhry S, Meade K, Lenoir M, Watson HG, Thyne S, Williams LK, Kumar R, Weiss KB, Grammer LC, Avila PC, Schleimer RP, Burchard EG, Brenner R.
Hum Mol Genetics 2008 Sep 1;17(17):2681-90.
Abstract: A highly heritable and reproducible measure of asthma severity is baseline pulmonary function. Pulmonary function is largely determined by airway smooth muscle (ASM) tone and contractility. The large conductance, voltage and calcium-activated potassium (BK) channel negatively regulates smooth muscle tone and contraction in ASM. The modulatory subunit of BK channels, the beta1-subunit, is critical for proper activation of BK channels in smooth muscle and has shown sex hormone specific regulation. We hypothesized that KCNMB1 genetic variants in African Americans may underlie differences in bronchial smooth muscle tone and thus pulmonary function, possibly in a sex-specific manner. Through resequencing of the KCNMB1 gene we identified several common variants including a novel African-specific coding polymorphism (C818T, R140W). The C818T SNP and four other KCNMB1 variants were genotyped in two independent groups of African American asthmatics (n = 509) and tested for association with the pulmonary function measure--forced expiratory volume (FEV(1)) % of predicted value. The 818T allele is associated with a clinically significant decline (-13%) in FEV(1) in both cohorts of asthmatics among males but not females (P(combined) = 0.0003). Patch clamp electrophysiology studies of the BK channel expressed with the 140Trp variant of the beta1-subunit demonstrated significantly reduced channel openings, predicted by the loss of pulmonary function observed. African American male asthmatics carrying the 818T allele (10% of population) are potentially at risk for greater airway obstruction and increased asthma morbidity. Female asthmatics may be insulated from the deleterious effects of the 818T allele by estrogen-mediated upregulation in BK channel activity.

Is ethnic self-identification a good predictor of health risks?

Ability of Ethnic Self-Identification to Partition Modifiable Health Risk Among US Residents of Mexican Ancestry.
Barger SD, Gallo LC.
Am J Public Health. 2008 Sep 17
Objectives. We examined the relationship between ethnic self-identification and the partitioning of health risk within a Mexican American population. Methods. We combined data from the 2000 to 2002 National Health Interview Surveys to obtain a large (N=10044) sample of US residents of Mexican ancestry. We evaluated health risk, defined as self-reported current smoking, overweight, and obesity, and compared the predictive strength of health risk correlates across self-identified Mexican and Mexican American participants. Results. Self-identified Mexican participants were less likely to smoke (odds ratio [OR]=0.70; 95% confidence interval[CI] = 0.60, 0.83; P<.001) and to be obese (OR=0.66; 95% CI=0.56, 0.77; P<.001) than were self-identified Mexican American participants. Within-group analyses found that sociodemographic predictors had inconsistent and even contradictory patterns of association with health risk across the 2 subgroups. Health risk was consistently lower among immigrants relative to US-born participants. Ethnic self-identification effects were independent of socioeconomic status. Conclusions. US residents of Mexican ancestry showed substantial within-group differences in health risk and risk correlates. Ethnic self-identification is a promising strategy to clarify differential risk and may help resolve apparent discrepancies in health risk correlates in this literature.
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