Archiver > Y-DNA-HAPLOGROUP-I > 2009-02 > 1233500583

From: William Morrow <>
Subject: Re: [yDNAhgI] Preliminary Summary of New HIV-HG I Study
Date: Sun, 1 Feb 2009 07:03:03 -0800 (PST)
In-Reply-To: <BLU146-W101DEFF9297963E832EFBCB8C40@phx.gbl>

In my younger days I was brown haired, green eyed, now have
white white hair and equally white beard and was proud of my Hg I
ethnic origins...in 2003 FTDNA emailed that my ancient ethnic
origins were Nordic but now I believe my subclade P37.2+*-Western
is more germanic than Nordic..because of my light complexion I have
had numerous (at least a hundred or so) skin cancers removed from
my face, neck and chest over the years. Don't like to think what's
going on inside my body...
But what saddened me most from this report was that Hg I folks
might be headed to extinction (survival of the fittest).  Maybe I'm
being too much of an alarmist?
Bill Morrow

--- On Sat, 1/31/09, Aaron Hill <> wrote:

From: Aaron Hill <>
Subject: [yDNAhgI] Preliminary Summary of New HIV-HG I Study
Date: Saturday, January 31, 2009, 8:43 PM

Study Finds Infectious Disease-DNA Connection
Y Chromosome Haplogroup I Shows Greater Risk

Here is my preliminary summary of the key points in the new HIV-HG I study.
Someone at NIH (National Institutes on Health) sent me a copy. They claim to
have identified a genetic relationship between men of northern European descent,
specifically those in haplogroup I, and HIV (“Association of Y chromosome
haplogroup I with HIV progression, and HAART outcome”). This study is personal
for me as my own yDNA (Y chromosome) is I1. The major mutation for this group is
known as M253.

The study focused on haplogroups I, R and F* in Americans of European descent,
and I, R and E in Americans with African ancestors. The researchers declared
finding “a unique association between infectious disease and the Y chromosome
haplogroup I.”

“Variation on the human Y chromosome is shaped by mutations ranging from
single nucleotide changes to inversions, duplications, and deletions, causing
larger structural changes that generate copy number variations ... Some of these
[mutations] have been linked to diseases such as oligo/azospermia and
gonadoblastoma, and shown to be represented frequently at certain Y haplogroups.
However, no such mutation or structural change has been documented to be
particularly associated with the Y-I haplogroup.”

The authors claimed the “study is the first to examine whether major Y
haplogroups have an association with HIV infection and progression to AIDS”
and that “the consistency of these results points to a significant role for
the Y chromosome in human health ... An independent analysis of AIDS-related
illnesses also suggests the increased risk of the Y-I haplogroup in all disease

“After some promising results were obtained for haplogroup I (Y-I),
additional markers, M253, M227, P37, M26, and M223 were genotyped to define
I1a*, I1a4, I1b*, I1b2, and I1c subhaplogroups (the corresponding YCC 2008 ...
names are I1, I1b, I2a, I2a2 and I2b, respectively). The remaining Y-I
haplogroup subjects who lacked the derived alleles at these markers were
assigned into the I* (xI1a*, xI1a4, xI1b*, xI1b2, xI1c) paragroup.”

The report noted that a “faster disease progression in the Y-I haplogroup
subjects was evident.” The “Cox model ... indicated that Y-I haplogroup
subjects depleted CD4 cells more quickly ... and progressed to AIDS ... and
death ... faster in the latter phase. The ... results were significant after
multiple test corrections among the Y-I haplogroup individuals.”

“The Cox analyses suggested a relatively faster progression signal for the
relatively common I1a* (I1) subhaplogroup compared to the other subhaplogroups.
However, a Kaplan–Meier survival analysis did not find significant differences
between the subhaplogroups indicating that the Y-I haplogroup as a whole best
explains the acceleration to AIDS outcomes rather than any particular Y-I

The study identified two possible explanations. A locus (or loci) on the Y
chromosome could be responsible for the quicker onset of AIDS.

“As our results do not indicate an infection difference between the
haplogroups, this locus might influence the AIDS progression pathway and lead to
faster immunosuppression and AIDS outcomes.”

An alternative is the possibility of an autosomal locus linked with haplogroup

“In European Americans, many ARG polymorphisms [AIDS restriction genes] have
been identified and found to influence HIV-1 infection.”

Yet, the researchers appeared to favor one theory, the Y chromosome.

“[O]utcomes observed in the Y-I haplogroup and the independence of the Y
chromosome effect from that of the examined autosomal loci suggest a causal
variant at a locus on the Y-I haplogroup ... So while a “winners curse” may
be inflating these estimates, the consistency of these results points to a
significant role for the Y chromosome in human health.”

“We also examined the frequency of Y chromosome haplogroups among subjects
with different AIDS-defining illnesses. An analysis of haplogroup frequencies
among cases and controls for AIDS-defining disease revealed a trend toward
elevated frequency of Y-I haplogroup cases compared to [others] for all of the
eight disease categories examined and a trend toward elevated malignancy
development and Kaposi sarcoma for the Y-I haplogroup. These findings were
consistent with a faster AIDS progression observed in the Y-I haplogroup
subjects. A similar analysis of AIDS-defining disease as the first outcome
showed seven of the eight disease categories with elevated Y-I haplogroup
frequencies. However, neither the results nor the Cox models for specific
disease outcomes were significant.”

The I subhaplogroups showed the same trend, but this was not due to a single
subhaplogroup. Overall, more individuals within the I haplogroup had an
increased chance of drug therapy (HAART) failure. In other words, medications,
specifically antiretroviral, did not work at a greater rate than the general

“The early and initial stages of AIDS development indicated by the HIV-1
infection rate and plasma viral load levels, in the I, R, and F* haplogroups
were not significantly different from each other. However, the Y-I haplogroup
showed significantly longer HIV-1 viral suppression time and higher failure rate
in HAART, outcomes that relate to later stages in AIDS progression. Moreover,
the significant results after false-discovery-rate corrections for AIDS-1987,
AIDS-related death, and HIV-1 viral suppression analyses suggest a potential
biological basis for these observations. An independent analysis of AIDS-related
illnesses also suggests the increased risk of the Y-I haplogroup in all disease

(Note that all emphasis in bold type and links are my own.)

-- Aaron
Windows Live™ Hotmail®:…more than just e-mail.

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