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Background: Per- and poly-fluoroalkyl substances (PFAS) are public health concerns because of widespread exposure through contaminated foods/drinking water. Although some determinants of PFAS exposure have been suggested, the role of geographic location and race/ethnicity in PFAS exposure has not been well characterized., Objectives: We examined potential determinants of PFAS from the Study of Women's Health Across the Nation (SWAN)., Methods: This study includes 1302 women aged 45-56 years from 5 SWAN sites where white women and women from one minority group were recruited (black from Southeast Michigan, Pittsburgh, Boston; Chinese from Oakland; Japanese from Los Angeles). We determined concentrations of 11 PFAS in serum samples collected in 1999-2000 and examined 7 PFAS detected in most women (>97%). Linear regression with backward elimination was used to identify important determinants of PFAS serum concentrations among a set of pre-specified variables (age, body mass index, site, race/ethnicity, education, financial hardship, occupation, born outside the United States (US), parity, menstrual bleeding within the past year, smoking status, alcohol consumption, and consumption of fish, dairy, pizza, salty snack, and French fries)., Results: Site and race/ethnicity were two major determinants of PFAS. White women had higher concentrations of linear perfluorooctanoic acid (PFOA) compared with the Chinese in Oakland (p < 0.0001) and blacks in Pittsburgh (p = 0.048). Black women in Southeast Michigan and Boston (vs. white women) had higher concentrations of linear (p < 0.001 for Southeast Michigan; p < 0.0001 for Boston) and total perfluorooctane sulfonic acid (PFOS) (p < 0.001 for both Southeast Michigan and Boston) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (p = 0.02 for Southeast Michigan; p < 0.001 for Boston). Chinese (Oakland) and Japanese (Los Angeles) women had higher concentrations of perfluorononanoic acid (PFNA) compared with white women in each site (p < 0.01 for both). Within white women, those in Pittsburgh had relatively higher concentrations of PFAS. Within Chinese and Japanese women, those who were born outside the US had significantly lower concentrations of most PFAS but significantly higher PFNA concentrations. Menstrual bleeding and parity were significantly associated with lower PFAS concentrations. Higher intake of salty snacks including popcorn was significantly associated with higher concentrations of linear PFOA, PFOS and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid., Discussion: Geographic locations and race/ethnicity play an important role in differential exposure to PFAS, with racial/ethnic burdens differing between PFOS, PFOA and PFNA. Menstruation and parity were also determinants of PFAS concentrations possibly as an elimination route., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk., Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided., Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0., Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Time-varying phenotypes have been studied less frequently in the context of genome-wide analyses across ethnicities, particularly for mood disorders. This study uses genome-wide association studies of depressive symptoms in a longitudinal framework and across multiple ethnicities to find common variants for depressive symptoms. Ethnicity-specific GWAS for depressive symptoms were conducted using three approaches: a baseline measure, longitudinal measures averaged over time, and a repeated measures analysis. We then used meta-analysis to jointly analyze the results across ethnicities within the Multi-ethnic Study of Atherosclerosis (MESA, n = 6,335), and then within ethnicity, across MESA and a sample from the Health and Retirement Study African- and European-Americans (HRS, n = 10,163)., Methods: This study uses genome-wide association studies of depressive symptoms in a longitudinal framework and across multiple ethnicities to find common variants for depressive symptoms. Ethnicity-specific GWAS for depressive symptoms were conducted using three approaches: a baseline measure, longitudinal measures averaged over time, and a repeated measures analysis. We then used meta-analysis to jointly analyze the results across ethnicities within the Multi-ethnic Study of Atherosclerosis (MESA, n = 6,335), and then within ethnicity, across MESA and a sample from the Health and Retirement Study African- and European-Americans (HRS, n = 10,163)., Results: Several novel variants were identified at the genome-wide suggestive level (5×10(-8) < p-value ≤ 5×10(-6)) in each ethnicity for each approach to analyzing depressive symptoms. The repeated measures analyses resulted in typically smaller p-values and an increase in the number of single-nucleotide polymorphisms (SNP) reaching genome-wide suggestive level., Conclusions: For phenotypes that vary over time, the detection of genetic predictors may be enhanced by repeated measures analyses.

Serum samples from eight endogamous Indian tribal populations of Madhya Pradesh (Dhurwa, Halba, Bhatra, Muria, Maria) and Orissa (Deshia Khond, Binjhal, Kisan) with a total of n = 731 unrelated individuals were typed for G1M (1,2,3,17), G3M (5,10,11,13,14,15,16,21, 26), and KM (1). In seven of these populations five different GM haplotypes were found: GM* 1,17;21,26; GM* 1,17;10,11,13,15,16; GM* 1,2, 17;21,26; GM* 1,3;5,10,11,13,14,26; and GM* 3;5,10,11,13,14,26. In the Kisan sample the haplotype GM* 1,2,17;21,26 is absent. The intergroup variability in the distribution of these haplotypes is considerable and statistically highly significant. The reasons for that can be attributed to the ethnohistory and to the genetic isolation of these eight endogamous tribal populations. The GM haplotype distribution pattern of all these groups is quite different from that of the non-tribal populations of India, whereas it is in good agreement with that of the so far tested other tribal populations from India. This can be explained by different origin and history of the Indian tribal and non-tribal populations. In the KM system, too, remarkable variability is seen in the distribution of phenotype and allele frequencies among the eight tribal populations under study.

Genetic polymorphisms for six blood groups, three red cell enzymes, three serum proteins, and hemoglobin were examined in sixteen central Indian tribal populations. Nine of the tribes belonged to Orissa, five to Madhya Pradesh, and two to Maharashtra. Eleven tribes spoke the Dravidian language, three Indo-Ayran, and two the language of the Austro-Asiatic families. The population structure of these tribal populations was analyzed at the inter- and intrastate and linguistic levels, using data for 13 genetic systems (38 alleles or haplotypes). Nine of the 13 loci showed significant heterogeneity in the 16 tribes, and the pattern of heterogeneity was also discernible in the different states and in the Dravidian-speaking tribes. As expected, the extent of genetic differentiation or gene diversity was the highest so far reported from central India. The mean FIS and HS for each locus in the different state, linguistic, and total tribal groups were consistently higher than the FST and GST values, respectively, showing that the genetic structure of each tribe is highly influenced by inbreeding. In a genetic affinity analysis by genetic distance the Indo-Aryan and Austro-Asiatic language groups showed little affinity with each other, although there was some tendency toward geographic affinity. The present analysis indicates that, in addition to genetic drift, gene flow, and selection, the genetic structure of the populations of central India is also highly influenced by sociocultural adaptation and inbreeding.

Spatial autocorrelation analysis performed on published data pertaining to caste and tribal populations of the Indian subcontinent has revealed that the surfaces of A, B and O allele frequencies are highly fractured. The only significant spatial autocorrelation was observed in respect of the A allele frequency among caste populations.

In July-November, 1986, Saryupari Brahmins of Chhattisgarh (Central India) have been investigated for the distribution of ABO blood groups, Rh factor, ABH secretion, PTC taste sensitivity and seven morphological traits. The important findings in brief are as follows: 1. The frequency of O blood group is slightly dominant (38.91%) and gene frequency exhibit r > q > p pattern. Statistical analysis (D/sigma = 0.5447) show that the population is in genetic equilibrium. 2. Estimation of the expected rate of erythroblastosis foetalis occurred in this population is calculated to be 8-16 cases in every 10,000 pregnancies. 3. High incidence (53.82%) of non-secretors of ABH substances in saliva suggest that this group may belong to Caucasoid stock. 4. The ability to taste the chemical PTC has a high frequency (61.81%) in this group. 5. R/L type of handclasping (58.15%), leg folding (65.38%) and L/R type of arm folding (58.93%) is dominant. L-type of handedness (5.48%) is moderately high. 6. Tongue rollers (93.28%) and folders (53.77%) are more among them. 7. Free type of ear lobe (68.68%) is the common feature in this population. 8. The above observations were compared in details with other Brahmin populations reported from India with special reference to the descendant groups residing in Madhya Pradesh (Central India). Furthermore, the results obtained on growth studies, and dermatoglyphic studies (palm and sole) from our published literature were also included so as to have some idea on the genetical, behavioural, dermatoglyphic and growth norms of this group.

A survey was conducted to study the genetic differentiation among 16 tribal groups of Orissa, Madhya Pradesh, and Maharashtra belonging to different ethnic and linguistic affiliations. Sixteen hundred and fifteen blood samples from both sexes were tested for 5 red cell enzyme systems: ACP, ESD, PGD, GLO, LDH, and Hb pattern. Three hundred and nineteen male individuals were tested for G-6-PD enzyme deficiency. The distribution of the enzyme markers and Hb show a range of variation which are more or less within the Indian range. Cases of homozygous HbSS were detected in all the tribes except 3 tribes in Orissa. Two cases of LDH Cal-1 homozygote were found in two Dravidian language speaking Orissa tribes. The chi 2-values for testing the homogeneity of gene frequencies indicate a non-significant heterogeneity for all alleles in the individual system. Within population diversity seems to be larger than between population diversity. The degree of over all genetic differentiation as measured by GST value is 0.0154 +/- 0.0071.

Sixteen tribal populations from Orissa, Madhya Pradesh and Maharashtra have been typed for the polymorphic blood group systems A1A2B0, MNSs, Rhesus, Kell, Duffy and Diego. The heterogeneity in the distribution of haplotype and allele frequencies, respectively, is partly considerable. It is supposed that this is due to the operation of several microevolutionary factors, such as genetic drift, social and geographic isolation and gene flow. This is discussed in detail.

Four-hundred fifty-nine people, including 106 Santals, 43 Bhuiyas, 107 Sakaldipi Brahmins, 108 Chamars, and 95 Ansari Muslims, of the Giridhi district of Bihar have been tested for transferrin, group-specific component, phosphoglucomutase subtypes, and glyoxalase-I, 6-phosphogluconate dehydrogenase, and adenylate kinase types. Genetic distance estimates by both dendrogram and principal component methods for these 5 populations and the Oraons on the basis of 19 alleles at 6 polymorphic loci indicate 2 major clusters: Brahmins and Muslims, the latter of which is composed of two subclusters (Santals and Bhuiyas, and Oraons and Chamars). The Santal and Bhuiya tribes both speak Mundari, whereas the Oraons speak a Dravidian language. The Chamars, although low-caste Hindus, seem to have a non-Europoid origin, as do the Oraons.

Three populations (Poliya, Deshi, and Tiyor) of the Koch ethnic group have been studied for the distribution of three serum protein and four red cell enzyme polymorphisms. There was no significant difference in the allelic frequencies of these systems in the three populations of the Koch ethnic group. The overall gene frequencies were as follows: Hp1, 0.21; Gc1F, 0.34; Gc1S, 0.36; Gc2, 0.30; TfC1, 0.66; TfC2, 0.26; TfC3, 0.001; TfD, 0.06; GLO1, 0.21; PGI2, 0.04; AK2, 0.01; PGM1+, 0.80; PGM1-, 0.06; PGM2+, 0.11 and PGM2-, 0.02. The phenotypic distribution at all the loci was at Hardy-Weinberg equilibrium.

Phenotype and gene frequencies for four blood group systems (ABO, MN, Rh and P) and haptoglobin among five endogamous groups of Delhi, India, are reported. All the systems are polymorphic in all the population groups. The average heterozygosity per locus in high (in the range 48-52 per cent) for all the groups. The extent of genic variability among the groups in terms of net codon differences per locus has been studied; the heterogeneity within the groups is large as compared to the between-group heterogeneity. There is no definite clustering of the of the groups with respect to their biological rank.

Ten endogamous population groups of West Bengal (India)--Rabhas, Garos, Mechs, Rajbanshis, Jalia Kaibartas, Bagdis, Lodhas, Mundas, Brahmins, Vaidyas--have been typed for twelve polymorphic systems: ABO, Gm, Km, Hp, Cp, Tf, Alb, Hb, aP, EsD, AK and PGM1. The results are compared with those obtained on other Indian populations. Serological and anthropometric data, which have been included into population comparisons, reveal a considerable genetic variability of the groups under study. This variability is obviously connected with the population history of West Bengal.

The ABO and Rh (D) blood groups have been examined in 568 individuals of 4 endogamous groups, viz, Mala, Yerukula, Kapu and Vadagalai Ayangar Brahmin. In the ABO blood group system, all the other groups except for the Yerukula show the general Asiatic trend (O greater than B greater than A). All individuals examined among the Vadagalai Ayangar Brahmins were Rh (D)-positive. Other populations show a low frequency of d allele.

798 placentas (Brahmin 141, Kayastha 303, Mahishya 91 and mixed low castes 263), from Calcutta hospitals, have been studied by starch gel electrophoresis for alkaline phosphatase types. The estimated gene-frequencies resemble those found else-where in caucasoid populations. Statistically significant differences (P approximately 0.02) were, however, noticed between the broadly divided upper caste group (Brahmin and Kayastha) and the lower caste group (Mahishya and mixed low castes) in respect of Plf 1 and Pls 1) gene distributions. The upper caste group has higher Plf 1 and lower Pls 1 frequencies than the lower caste group. The two broad caste groups are, however, quite uniform in Pli 1 distribution. All the six common phenotypes (S1, F1, I 1, S1F1, S1 I 1 and F1 I 1) and seven rare phenotypes (S1S2, S1S3, F1F2, F1S2, F2S1, F1S3 and I 1S2) were found.

The four endogamous groups of fishermen living around the city of Puri, located on the eastern coast of India, were studied for blood groups, red cell enzymes and serum proteins (11 loci). Only 1.3% of the total diversity among the groups studied is due to differences between them (GST = 0.013). The genetic distances between populations were estimated using Edwards and Cavalli-Sforza's method. The pattern of genetic distance reflects the geographical distribution of these groups. In general, these observations support the patterns of variation based on anthropometric and dermatoglyphic variables.

Genetic polymorphism of 16 red-cell antigens, enzymes, serum proteins and Hb variants was investigated in 214 male and female individuals belonging to the Meiteis and a Brahmin caste group living in Imphal (Manipur, Northeast India). Ethnohistorical records suggest that the Meiteis are of Mongoloid origin, while the original Brahmin settlers represent the easternmost part of the so-called Caucasoids. The markers studied are: A1A2BO, MNSs, Rh-system, Duffy, Diego; Gm, Km, Gc, Hp, Tf, Cp; Hb; aP, AK, EsD and LDH. The comparison between the two groups on the basis of the markers studied showed that the Meiteis and Brahmins are very close to each other with respect to most of the loci except Gm, EsD and Hb, where significant statistical differences were found.